Biomedical subjects

B J Casey

Publications and source records attributed to B J Casey.

At least 37 records · Page 2Linked to original sources

PubMed2005

Intentional false responding shares neural substrates with response conflict and cognitive control.

The ability to deceive others is a high-level social and cognitive function. It has been suggested that response conflict and cognitive control increase during deceptive acts but this hypothesis has not been evaluated directly. Using fMRI, we tested this prediction for the execution of an intentional false response. Subjects were instructed to respond truthfully or falsely to a series of yes/no questions that were also varied in autobiographical and nonautobiographical content to further examine the influence of personal relevance when lying. We observed an interference effect (longer reaction times for false versus true responses) that was accompanied by increased activation within the anterior cingulate, caudate and thalamic nuclei, and dorsolateral prefrontal cortex (DLPFC), a circuit that has been implicated in response conflict and cognitive control. Behavioral and neural effects were more robust when falsifying autobiographical responses relative to nonautobiographical responses. Furthermore, a correlation between reaction time and left caudate activity supported the presence of increased response inhibition when falsifying responses. When presented with self-relevant (autobiographical) stimuli regardless of response condition, the mesial prefrontal and posterior cingulate cortices were recruited. Neural activity within these two regions and the anterior cingulate cortex (ACC) also showed correlations with self-report personality measures from the Psychopathic Personality Inventory (PPI). Overall, we conclude that the process of interference is inherent to the act of falsifying information and that the amount of conflict induced and cognitive control needed to successfully execute false responses is greater when dealing with personal information.

Adult↗

PubMed2005

Altered emotional processing in pediatric anxiety, depression, and comorbid anxiety-depression.

The goal of this study was to examine some of the mechanisms underlying emotion regulation in childhood affective disorders by examining the impact of distracting emotional information during performance on a working memory task ("Emotional n-back" or E-n-back). The sample included 75 children (38 girls and 37 boys) between 8 and 16 years of age meeting criteria for: Anxiety disorder (ANX, n = 17), Major depressive disorder (MDD, n = 16), Comorbid anxiety and depression (CAD, n = 24), or Low-risk normal control (LRNC, n = 18). Results showed that the MDD and CAD groups had significantly longer reaction times on negative emotional backgrounds compared to neutral backgrounds, whereas the LRNC group had significantly longer reaction times on positive backgrounds. These results suggest altered processing of emotional information particularly associated with depression. Because the E-n-back task engages higher-order cognitive processes, these results suggest that these alterations in processing emotional information also interfere with the cognitive processes that govern how attentional resources are allocated. Further, research is needed to replicate this study and delineate underlying neural mechanisms.

Adolescent↗

PubMed2005

Changes in cerebral functional organization during cognitive development.

It has been just under a decade since contemporary neuroimaging tools, such as functional magnetic resonance imaging, were first applied to developmental questions. These tools provide invaluable information on how brain anatomy, function and connectivity change during development. Studies using these methods with children and adolescents show that brain regions that support motor and sensory function mature earliest, whereas higher-order association areas, such as the prefrontal cortex, which integrate these functions, mature later.

Cerebral Cortex↗

PubMed2005

Imaging the developing brain: what have we learned about cognitive development?

The human brain undergoes significant changes in both its structural architecture and functional organization across the life span. Advances in neuroimaging techniques over the past decade have allowed us to track these changes safely in the human in vivo. We review the imaging literature on the neurobiology of cognitive development, focusing specifically on cognitive task-dependent changes observed in brain physiology and anatomy across childhood and adolescence. The findings suggest that cortical function becomes fine-tuned with development. Brain regions associated with more basic functions such as sensory and motor processes mature first, followed by association areas involved in top-down control of behavior.

Adolescent↗

PubMed2005

An integrative theory of attention-deficit/ hyperactivity disorder based on the cognitive and affective neurosciences.

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral syndrome that arises in early childhood, often co-occurs with conduct disorder and leads, developmentally, to antisocial behavior and substance abuse. Models from cognitive and affective neuroscience have been invoked in an effort to understand the development of ADHD, leading to a broad array of interrelated theories and hypothesized mechanisms. In this paper, we highlight core mechanisms that may cut across several theories and constructs, and thus provide some leverage for further study and conceptualization from a neuroscience perspective. We emphasize the joint operations of frontostriatal and frontocerebellar neural loops in detecting and predicting what and when important events in the environment will occur and their interaction with frontoamygdala loops in assigning emotional significance to these events. We note that weaknesses in the development of these basic operations could lead to decrement in the development of cognitive and affective control and other mental operations mediated by prefrontal cortex during development. In turn, such decrement could lead to many of the phenotypic cognitive and neuropsychological features seen in children with ADHD.

Affect↗

PubMed2005

Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls.

Genetic influences on behavior are complex and, as such, the effect of any single gene is likely to be modest. Neuroimaging measures may serve as a biological intermediate phenotype to investigate the effect of genes on human behavior. In particular, it is possible to constrain investigations by prior knowledge of gene characteristics and by including samples of subjects where the distribution of phenotypic variance is both wide and under heritable influences. Here, we use this approach to show a dissociation between the effects of two dopamine genes that are differentially expressed in the brain. We show that the DAT1 gene, a gene expressed predominantly in the basal ganglia, preferentially influences caudate volume, whereas the DRD4 gene, a gene expressed predominantly in the prefrontal cortex, preferentially influences prefrontal gray matter volume in a sample of subjects including subjects with ADHD, their unaffected siblings, and healthy controls. This demonstrates that, by constraining our investigations by prior knowledge of gene expression, including samples in which the distribution of phenotypic variance is wide and under heritable influences, and by using intermediate phenotypes, such as neuroimaging, we may begin to map out the pathways by which genes influence behavior.

Adolescent↗

PubMed2005

Neuroscience perspectives on disparities in school readiness and cognitive achievement.

This article allows readers to look at racial and ethnic disparities in school readiness from a neuroscience perspective. Although researchers have traditionally measured gaps in school readiness using broad achievement tests, they can now assess readiness in terms of more specific brain-based cognitive functions. Three neurocognitive systems--cognitive control, learning and memory, and reading--are essential for success in school. Thanks to recent advances in brain imaging, it is now possible to examine these three systems, each located in specific areas of the brain, by observing them in action as children engage in particular tasks. Socioeconomic status--already linked with how well children do on skills tests generally--is particularly closely linked with how well they perform on tasks involving these crucial neurocognitive systems. Moreover, children's life experiences can influence their neurocognitive development and lead to functional and anatomical changes in their brains. Noting that chronic stress or abuse in childhood can impair development of the brain region involved in learning and memory, the authors show how the extreme stress of being placed in an orphanage leads to abnormal brain development and decreased cognitive functioning. More optimistically, the authors explain that children's brains remain plastic and capable of growth and development. Targeted educational interventions thus have the promise of improving both brain function and behavior. Several such interventions, for example, both raise children's scores in tests of reading and increase activity in the brain regions most closely linked with reading. The brain regions most crucial for school readiness may prove quite responsive to effective therapeutic interventions-even making it possible to tailor particular interventions for individual children. The authors look ahead to the day when effective educational interventions can begin to close racial and socioeconomic gaps in readiness and achievement.

Brain↗

PubMed2005

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.

Adolescent↗

PubMed2004

Opiate addicts lack error-dependent activation of rostral anterior cingulate.

BACKGROUND: Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets. Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and, given generally poorer performance on such tasks by addicts, whether this signal is disrupted in addiction. METHODS: We used rapid, event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task. RESULTS: Compared with controls, opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance. In controls, the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance, particularly sensitivity in discriminating targets from nontargets. CONCLUSIONS: The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior.

Adult↗

PubMed2004

Differential cingulate and caudate activation following unexpected nonrewarding stimuli.

This study examined the effects of varying the predictability of nonrewarding events on behavior and neural activation using a rapid mixed-trial functional magnetic resonance imagery (fMRI) design. Twelve adult subjects were scanned with echo planar imaging during performance of a visual detection task where the probability of events (target and nontarget) varied. This task included expected and unexpected nonrewarding events (expected target, unexpected nontarget, and omission of target) in a design that closely parallels studies of dopamine function and reward processing in the alert monkey. We predicted that activation in dopamine-rich areas of the forebrain would behave like the animal literature shows that dopamine neurons in the midbrain behave. Specifically, we predicted increased activity in these regions when an unexpected event occurred and decreased activity when an expected event was omitted. Two main regions, the anterior cingulate and dorsal striatum, showed this pattern. The response in these regions was distinguished by enhanced anterior cingulate activity following the occurrence of an unexpected event and greater suppression of caudate activity following the omission of an expected event. These results suggest that neural activity within specific dopamine-rich brain regions can be modulated by violations in the expectation of nonrewarding events and that the direction of the modulation depends on the nature of the violations.

Adult↗

PubMed2004

Developmental cognitive neuroscience: progress and potential.

Developmental cognitive neuroscience is an evolving field that investigates the relations between neural and cognitive development. Lying at the intersection of diverse disciplines, work in this area promises to shed light on classic developmental questions, mechanisms subserving developmental change, diagnosis and treatment of developmental disorders, and cognitive and neuroscientific topics traditionally considered outside the domain of development. Fundamental questions include: What are the interrelations between developmental changes in the brain (e.g. in connectivity, chemistry, morphology) and developmental changes in children's behavior and cognitive abilities (e.g. representational complexity, ability to sustain selective attention, speed of processing)? Why, and how, is learning enhanced during certain periods in development? How is our knowledge organized, and how does this change with development? We discuss preliminary investigations of such questions and directions for future work.

Aptitude↗

PubMed2004

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.

Adolescent↗

PubMed2003

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.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Brain plasticity, learning, and developmental disabilities.

This is a time of significant gains in methodological development for examining the developing human brain. New efforts are underway to unify the understanding of the development of brain anatomy with physiological, cellular and molecular processes that influence behavioral development. This special issue provides animal models of behavior and brain development, applications of noninvasive imaging and genetic methods to human brain development and behavior, and select reviews of how these models and methods have been applied to the examination of developmental disabilities. This issue reflects a sampling of current approaches to the study of brain plasticity, development and learning in typically and atypically developing humans and animals.

Brain↗

PubMed2003

Imaging the developing brain with fMRI.

Advancements in magnetic imaging techniques have revolutionized our ability to study the developing human brain in vivo. The ability to noninvasively image both anatomy and function in healthy volunteers, including young children, has already enhanced our understanding of brain and behavior relations. The application of these techniques to developmental research offers the opportunity to further explore these relationships and allows us to ask questions about where, when and how cognitive abilities develop in relation to changes in underlying brain systems. It is also possible to explore the contributions of maturation versus learning in the development of these abilities through cross-sectional and longitudinal research involving training and intervention procedures. Current imaging methodologies, in conjunction with new and rapidly evolving techniques, hold the promise of even greater insights into developmental issues in the near future. These methodologies and their application to development and learning are discussed in the current paper.

Adult↗

PubMed2003

Parametric manipulation of conflict and response competition using rapid mixed-trial event-related fMRI.

In the current study we examined the influence of preceding context on attentional conflict and response competition using a flanker paradigm. Nine healthy right-handed adults participated in a rapid mixed trial event-related functional magnetic resonance imaging (fMRI) study, in which increasing numbers of either compatible or incompatible trials preceded an incompatible trial. Behaviorally, reaction times on incompatible trials increased as a function of the number of preceding compatible trials. Several brain regions showed monotonic changes to the preceding context manipulation. The most common pattern was observed in anterior cingulate, dorsolateral prefrontal, and superior parietal regions. These areas showed an increase in activity for incompatible trials as the number of preceding compatible trials increased and a decrease in activity for incompatible trials as the number of preceding incompatible trials increased. Post hoc analysis showed that while the MR signal in the anterior cingulate and dorsolateral prefrontal regions peaked before the superior parietal region, the dorsolateral prefrontal MR signal peaked early and remained at this level. These findings are consistent with the conflict monitoring theory that postulates that the anterior cingulate cortex detects or monitors conflict, while PFC is involved in control adjustments that may then lead to modulation of superior parietal cortex in top-down biasing of attention.

Adult↗

PubMed2003

Exploring genetic influences on cognition: emerging strategies for target validation and treatment optimization.

Genomic research has produced an abundance of new candidate targets that remain to be validated as potential treatments for neuropsychiatric disorders. Functional neuroimaging, meanwhile, has provided detailed new insights into the neural circuits involved in emotional and cognitive control. At the growing interface between these independent lines of progress, new efforts are underway to unify our understanding of regional brain function with that of genetic and biochemical influences on behavior. Such a unified understanding of the mechanisms involved in cognitive and emotional control may open up new avenues for therapeutic intervention at the pharmacological and behavioral levels. In line with this, a new initiative sponsored by the National Institutes of Mental Health (NIMH) aims to bridge gaps between clinical diagnostics and the molecular processes that influence susceptibility to psychiatric disorders. A major goal of this initiative is to identify the neural and neurochemical substrates of basic cognitive processes that are disrupted in psychiatric disorders and to examine the influence of genetic factors at the cognitive level. This review describes some well-known findings that are at the forefront of this interface. The progress already made indicates that the goals of the new initiative are well founded and achievable.

Animals↗

PubMed2002

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.

Adult↗