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1.  The Dopamine Receptor D4 Gene 7-Repeat Allele Interacts with Parenting Quality to Predict Effortful Control in Four-Year-Old Children 
Child development research  2012;2012:863242-.
The dopamine receptor D4 gene (DRD4) 7-repeat allele has been found to interact with environmental factors such as parenting in children and peer attitudes in adults to influence aspects of behavior such as risk taking. We previously found that in toddlers, lower-quality parenting in combination with the 7-repeat allele of the DRD4 gene was associated with greater parent-reported Sensation Seeking (SS), but was unrelated to Effortful Control (EC). We now report findings from a followup assessment with the same sample of children showing that parenting quality interacts with the presence of the 7-repeat allele to predict EC in 3-to 4-year-old children. The change in these patterns of results may reflect the increased role of the executive attention network in older children and adults. However, due to the small sample size (N = 52) and the novelty of the results, these findings should be treated with caution and considered preliminary until they are replicated in an independent sample.
PMCID: PMC3712539  PMID: 23869253
2.  Special issue on mindfulness neuroscience 
PMCID: PMC3541496  PMID: 22956677
3.  Tools of the trade: theory and method in mindfulness neuroscience 
Mindfulness neuroscience is an emerging research field that investigates the underlying mechanisms of different mindfulness practices, different stages and different states of practice as well as different effects of practice over the lifespan. Mindfulness neuroscience research integrates theory and methods from eastern contemplative traditions, western psychology and neuroscience, and from neuroimaging techniques, physiological measures and behavioral tests. We here review several key theoretical and methodological challenges in the empirical study of mindfulness neuroscience and provide suggestions for overcoming these challenges.
PMCID: PMC3541497  PMID: 23081977
mindfulness neuroscience; mindfulness; meditation; neuroplasticity; gene-environment interaction
4.  Attentional Networks and Consciousness 
The term consciousness is an important one in the vernacular of the western literature in many fields. It is no wonder that scientists have assumed that consciousness will be found as a component of the human brain and that we will come to understand its neural basis. However, there is rather little in common between consciousness as the neurologist would use it to diagnose the vegetative state, how the feminist would use it to support raising male consciousness of the economic plight of women and as the philosopher would use it when defining the really hard question of the subjective state of awareness induced by sensory qualities. When faced with this kind of problem it is usual to subdivide the term into more manageable perhaps partly operational definitions. Three meanings that capture aspects of consciousness are: (1) the neurology of the state of mind allowing coherent orientation to time and place (2) the selection of sensory or memorial information for awareness and (3) the voluntary control over overt responses. In each of these cases the mechanisms of consciousness overlap with one or more of the attentional networks that have been studied with the methods of cognitive neuroscience. In this paper we explore the overlap and discuss how to exploit the growing knowledge of attentional networks to constrain ideas of consciousness.
PMCID: PMC3298960  PMID: 22416239
attention networks; alerting; orienting; executive
Neuroimage  2011;61(2):450-456.
The study of attention has largely been about how to select among the various sensory events but also involves the selection among conflicting actions. Prior to the late 1980s, locating bottlenecks between sensory input and response dominated these studies, a different view was that attentional limits involved the importance of maintaining behavioral coherence rather than resulting from a bottleneck. In both cases ideas of resource limits taken over from economics were important. Early evidence relating to the anatomy of attention came from neurological investigations of lesioned patients, but the major impetus for the anatomical approach came from neuroimaging studies that provided evidence of brain networks related to orienting to sensory events and control of response tendencies. The presence of a functional anatomy has supported studies of the development of attention networks and the role of neuromodulators and genetic poymorphisms in their construction. Together these developments have enhanced our understanding of attention and paved the way for significant applications to education, pathology and prevention of mental illness.
PMCID: PMC3345293  PMID: 22227132
6.  Neural correlates of establishing, maintaining, and switching brain states 
Trends in cognitive sciences  2012;16(6):330-337.
Although the study of brain states is an old one in neuroscience, there has been growing interest in brain state specification owing to MRI studies tracing brain connectivity at rest. In this review, we summarize recent research on three relatively well-described brain states: the resting, alert, and meditation states. We explore the neural correlates of maintaining a state or switching between states, and argue that the anterior cingulate cortex and striatum play a critical role in state maintenance, whereas the insula has a major role in switching between states. Brain state may serve as a predictor of performance in a variety of perceptual, memory, and problem solving tasks. Thus, understanding brain states is critical for understanding human performance.
PMCID: PMC3419378  PMID: 22613871
7.  Control Networks and Neuromodulators of Early Development1 
Developmental Psychology  2011;48(3):827-835.
In adults most cognitive and emotional self-regulation is carried out by a network of brain regions, including the anterior cingulate, insula and areas of the basal ganglia, related to executive attention. We propose that during infancy control systems depend primarily upon a brain network involved in orienting to sensory events that includes areas of the parietal lobe and frontal eye fields. Studies of human adults and alert monkeys show that the brain network involved in orienting to sensory events is moderated primarily by the nicotinic cholinergic system arising in the nucleus basalis. The executive attention network is primarily moderated by dopaminergic input from the ventral tegmental area. A change from cholinergic to dopaminergic modulation would be a consequence of this switch of control networks and may be important in understanding early development. We trace the attentional, emotional and behavioral changes in early development related to this developmental change in regulative networks and their modulators.
PMCID: PMC3253251  PMID: 21942663
8.  Variations in COMT Gene Interact With Parenting to Influence Attention in Early Development1 
Neuroscience  2009;164(1):121-130.
Attention influences many aspects of cognitive development. Variations in the COMT gene, known to affect dopamine neurotransmission, have frequently been found to influence attention in adults and older children. In this paper we examined 2 year old children and found that variation in the COMT gene influenced attention in a task involving looking to a sequence of visual stimuli. Because the influence of another dopamine related gene (DRD4) has been shown to interact with parenting quality at this age, we explored parenting in relation to variations in the COMT gene. Variations in COMT interacted with parenting quality to influence our attention measure. The Val108/158Met polymorphism of COMT is commonly used to determine allelic groups, but recently haplotypes of several polymorphisms within this gene have been shown to do a better job in reflecting perceived pain. Since attention and pain both involve the activation of the anterior cingulate gyrus in imaging studies, we compared the Val108/158Met influence with the COMT haplotypes and found the latter to be more predictive of attention. Our results confirm that important aspects of cognitive development including attention depend on the interaction of genes and early environment.
PMCID: PMC2760680  PMID: 19482061
9.  Toward A Physical Basis of Attention and Self Regulation1 
Physics of life reviews  2009;6(2):103-120.
The concept of self-regulation is central to the understanding of human development. Self-regulation allows effective socialization and predicts both psychological pathologies and levels of achievement in schools. What has been missing are neural mechanisms to provide understanding of the cellular and molecular basis for self-regulation. We show that self-regulation can be measured during childhood by parental reports and by self-reports of adolescents and adults. These reports are summarized by a higher order factor called effortful control, which reflects perceptions about the ability of a given person to regulate their behavior in accord with cultural norms. Throughout childhood effortful control is related to children’s performance in computerized conflict related tasks. Conflict tasks have been shown in neuroimaging studies to activate specific brain networks of executive attention. Several brain areas work together at rest and during cognitive tasks to regulate competing brain activity and thus control resulting behavior. The cellular structure of the anterior cingulate and insula contain cells, unique to humans and higher primates that provide strong links to remote brain areas. During conflict tasks, anterior cingulate activity is correlated with activity in remote sensory and emotional systems, depending upon the information selected for the task. During adolescence the structure and activity of the anterior cingulate has been found to be correlated with self-reports of effortful control.
Studies have provided a perspective on how genes and environment act to shape the executive attention network, providing a physical basis for self-regulation. The anterior cingulate is regulated by dopamine. Genes that influence dopamine levels in the CNS have been shown to influence the efficiency of self-regulation. For example, alleles of the COMT gene that influence the efficiency of dopamine transmission are related to the ability to resolve conflict. Humans with disorders involving deletion of this gene exhibit large deficits in self-regulation. Alleles of other genes influencing dopamine and serotonin transmission have also been found to influence ability to resolve conflict in cognitive tasks. However, as is the case for many genes, the effectiveness of COMT alleles in shaping self-regulation depends upon cultural influences such as parenting. Studies find that aspects of parenting quality and parent training can influence child behavior and the efficiency of self-regulation.
During development, the network that relates to self-regulation undergoes important changes in connectivity. Infants can use parts of the self-regulatory network to detect errors in sensory information, but the network does not yet have sufficient connectivity to organize brain activity in a coherent way. During middle childhood, along with increased projection cells involved in remote connections of dorsal anterior cingulate and prefrontal and parietal cortex, executive network connectivity increases and shifts from predominantly short to longer range connections. During this period specific exercises can influence network development and improve self-regulation. Understanding the physical basis of self-regulation has already cast light on individual differences in normal and pathological states and gives promise of allowing the design of methods to improve aspects of human development.
PMCID: PMC2748943  PMID: 20161073
Attention; genetic alleles; neural networks; self-regulation
10.  A Definitive Volume on Temperament 
PMCID: PMC3445045
11.  Expanding horizons in ergonomics research 
NeuroImage  2011;59(1):149-153.
PMCID: PMC3413260  PMID: 21816226
12.  The Attention System of the Human Brain: 20 Years After 
Here, we update our 1990 Annual Review of Neuroscience article, “The Attention System of the Human Brain.” The framework presented in the original article has helped to integrate behavioral, systems, cellular, and molecular approaches to common problems in attention research. Our framework has been both elaborated and expanded in subsequent years. Research on orienting and executive functions has supported the addition of new networks of brain regions. Developmental studies have shown important changes in control systems between infancy and childhood. In some cases, evidence has supported the role of specific genetic variations, often in conjunction with experience, that account for some of the individual differences in the efficiency of attentional networks. The findings have led to increased understanding of aspects of pathology and to some new interventions.
PMCID: PMC3413263  PMID: 22524787
alerting network; executive network; orienting network; cingulo-opercular network; frontoparietal network
13.  The impact of poverty on the development of brain networks 
Although the study of brain development in non-human animals is an old one, recent imaging methods have allowed non-invasive studies of the gray and white matter of the human brain over the lifespan. Classic animal studies show clearly that impoverished environments reduce cortical gray matter in relation to complex environments and cognitive and imaging studies in humans suggest which networks may be most influenced by poverty. Studies have been clear in showing the plasticity of many brain systems, but whether sensitivity to learning differs over the lifespan and for which networks is still unclear. A major task for current research is a successful integration of these methods to understand how development and learning shape the neural networks underlying achievements in literacy, numeracy, and attention. This paper seeks to foster further integration by reviewing the current state of knowledge relating brain changes to behavior and indicating possible future directions.
PMCID: PMC3421156  PMID: 22912613
childhood poverty; brain networks; plasticity; attention; literacy; numeracy
14.  Developing Mechanisms of Self-Regulation in Early Life 
Emotion review  2011;3(2):207-213.
Children show increasing control of emotions and behavior during their early years. Our studies suggest a shift in control from the brain's orienting network in infancy to the executive network by the age of 3–4 years. Our longitudinal study indicates that orienting influences both positive and negative affect, as measured by parent report in infancy. At 3–4 years of age, the dominant control of affect rests in a frontal brain network that involves the anterior cingulate gyrus. Connectivity of brain structures also changes from infancy to toddlerhood. Early connectivity of parietal and frontal areas is important in orienting; later connectivity involves midfrontal and anterior cingulate areas related to executive attention and self-regulation.
PMCID: PMC3164871  PMID: 21892360
attention; connectivity; development; orienting
15.  Brain states and hypnosis research✩,✩✩ 
Consciousness and cognition  2010;20(2):325-327.
Research in cognitive neuroscience now considers the state of the brain prior to the task an important aspect of performance. Hypnosis seems to alter the brain state in a way which allows external input to dominate over internal goals. We examine how normal development may illuminate the hypnotic state.
PMCID: PMC3164825  PMID: 20060745
16.  Timing the Brain: Mental Chronometry as a Tool in Neuroscience 
PLoS Biology  2005;3(2):e51.
Mental chronometry, which has origins dating back over a century, seeks to measure the time course of mental operations in the human nervous system
PMCID: PMC548951  PMID: 15719059
17.  Testing the behavioral interaction and integration of attentional networks 
Brain and cognition  2009;70(2):209-220.
One current conceptualization of attention subdivides it into functions of alerting, orienting, and executive control. Alerting describes the function of tonically maintaining the alert state and phasically responding to a warning signal. Automatic and voluntary orienting are involved in the selection of information among multiple sensory inputs. Executive control describes a set of more complex operations that includes monitoring and resolving conflicts in order to control thoughts or behaviors. Converging evidence supports this theory of attention by showing that each function appears to be subserved by anatomically distinct networks in the brain and differentially innervated by various neuromodulatory systems. Although much research has been dedicated to understanding the functional separation of these networks in both healthy and disease states, the interaction and integration among these networks still remain unclear. In this study, we aimed to characterize possible behavioral interaction and integration in healthy adult volunteers using a revised attentional network test (ANT-R) with cue-target interval and cue validity manipulations. We found that whereas alerting improves overall response speed, it exerts negative influence on executive control under certain conditions. A valid orienting cue enhances but an invalid cue diminishes the ability of executive control to overcome conflict. The results support the hypothesis of functional integration and interaction of these brain networks.
PMCID: PMC2674119  PMID: 19269079
attention; attentional networks; alerting; orienting; executive control
18.  Development of the time course for processing conflict: an event-related potentials study with 4 year olds and adults 
BMC Neuroscience  2004;5:39.
Tasks involving conflict are widely used to study executive attention. In the flanker task, a target stimulus is surrounded by distracting information that can be congruent or incongruent with the correct response. Developmental differences in the time course of brain activations involved in conflict processing were examined for 22 four year old children and 18 adults. Subjects performed a child-friendly flanker task while their brain activity was registered using a high-density electroencephalography system.
General differences were found in the amplitude and time course of event-related potentials (ERPs) between children and adults that are consistent with their differences in reaction time. In addition, the congruency of flankers affected both the amplitude and latency of some of the ERP components. These effects were delayed and sustained for longer periods of time in the children compared to the adults.
These differences constitute neural correlates of children's greater difficulty in monitoring and resolving conflict in this and similar tasks.
PMCID: PMC529252  PMID: 15500693
19.  Assessing the molecular genetics of attention networks 
BMC Neuroscience  2002;3:14.
Current efforts to study the genetic underpinnings of higher brain functions have been lacking appropriate phenotypes to describe cognition. One of the problems is that many cognitive concepts for which there is a single word (e.g. attention) have been shown to be related to several anatomical networks. Recently, we have developed an Attention Network Test (ANT) that provides a separate measure for each of three anatomically defined attention networks.
In this study we have measured the efficiency of neural networks related to aspects of attention using the ANT in a population of 200 adult subjects. We then examined genetic polymorphisms in four candidate genes (DRD4, DAT, COMT and MAOA) that have been shown to contribute to the risk of developing various psychiatric disorders where attention is disrupted. We find modest associations of several polymorphisms with the efficiency of executive attention but not with overall performance measures such as reaction time.
These results suggest that genetic variation may underlie inter-subject variation in the efficiency of executive attention. This study also shows that genetic influences on executive attention may be specific to certain anatomical networks rather than affecting performance in a global or non-specific manner. Lastly, this study further validates the ANT as an endophenotypic assay suitable for assessing how genes influence certain anatomical networks that may be disrupted in various psychiatric disorders.
PMCID: PMC130047  PMID: 12366871
20.  Assessing the heritability of attentional networks 
BMC Neuroscience  2001;2:14.
Current efforts to study the genetics of higher functions have been lacking appropriate phenotypes to describe cognition. One of the problems is that many cognitive concepts for which there is a single word (e.g. attention) have been shown to be related to several anatomical networks. Recently we have developed an Attention Network Test (ANT) that provides a separate measure for each of three anatomically defined attention networks. In this small scale study, we ran 26 pairs of MZ and DZ twins in an effort to determine if any of these networks show sufficient evidence of heritability to warrant further exploration of their genetic basis.
The efficiency of the executive attention network, that mediates stimulus and response conflict, shows sufficient heritability to warrant further study. Alerting and overall reaction time show some evidence for heritability and in our study the orienting network shows no evidence of heritability.
These results suggest that genetic variation contributes to normal individual differences in higher order executive attention involving dopamine rich frontal areas including the anterior cingulate. At least the executive portion of the ANT may serve as a valid endophenotype for larger twin studies and subsequent molecular genetic analysis in normal subject populations.
PMCID: PMC57000  PMID: 11580865

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