Variations in catechol-O-methyltransferase gene interact with parenting to influence attention in early development.

Attention influences many aspects of cognitive development. Variations in the catechol-O-methyltransferase (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 Val(108/158)Met polymorphism of COMT is commonly used to determine allelic groups, but recently haplotypes of several polymorphisms within this gene have been shown to be more strongly associated with perceived pain. Since attention and pain both involve the activation of the anterior cingulate gyrus in imaging studies, we compared the Val(108/158)Met 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.

[Attention and executive functions in patients with severe obesity. A controlled study using the Attention Network Test]. / Aufmerksamkeit und exekutive Funktionen bei Patienten mit Adipositas per magna. Eine kontrollierte Studie mit dem Aufmerksamkeitsnetzwerktest.

In this paper, attention and temperament are compared between 41 severely obese patients with psychiatric comorbidity and 45 control persons. Networks of attention were assessed by the Attention Network Test: alerting (ability to achieve and maintain an alert state), orienting (ability to orient to a stimulus), and executive attention (ability to resolve conflict). According to hypotheses, obese patients show reduced executive attention, more effortful control, and higher negative affectivity than controls. The concept of attention networks is related to cognitive mechanisms of self-regulation, opening new perspectives for understanding psychiatric disorders.

Assessing the heritability of attentional networks.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

Exploring the biology of socialization.

How will the social sciences take advantage of the revolution that has taken place in biology during the past two decades? Over the last fifteen years, neuroimaging has allowed the study of human cognition and emotion within psychology to achieve close alliances with biology through the development of cognitive and affective neuroscience. There is little doubt that a similar alliance between psychology and biology will occur in the domain of human brain development. In principle, understanding how the human brain is organized by experience (epigenetic rules) and how societies instruct their young could produce a link between natural and social science. The late David C. McClelland sought methods to base the social sciences on psychological ideas. McClelland sought to connect the values of achievement and power as coded from children's readers and popular ballads to societal economic growth and conflict. These efforts lacked knowledge of brain mechanisms of memory and attention and an understanding of the role of experience in organizing brain circuitry. Understanding of cognitive and brain systems related to knowledge and action may allow a new approach to forging connections between individual minds and social behavior.

Progress in the neural sciences in the the century after Cajal (and the mysteries that remain).

One hundred years after Santiago Ramon y Cajal provided critical evidence for the "neuron doctrine," his cellular view of the brain remains the basis of modern neural science. This article begins with a review of how the early work of Ramon y Cajal, Charles Sherrington, and John Eccles and their contemporaries laid the groundwork for our current understanding of he information processing of neural systems and for understanding the task faced by studies of how the brain develops. The visual system is examined in some detail as a model for experimental investigation into the structure, operational mechanisms, and functions of large neural systems. Discussion of the phenomena of visual awareness and consciousness, links between the visual system and other brain systems, and disorders that disrupt voluntary control of cognition and emotion lead to a broader consideration of the problem of consciousness.

Brain imaging of attentional networks in normal and pathological states.

The ability to image the human brain has provided a new perspective for neuropsychologists in their efforts to understand, diagnose, and treat insults to the human brain that might occur as the result of stroke, tumor, traumatic injury, degenerative disease, or errors in development. These new findings are the major theme of this special issue. In our article, we consider brain networks that carry out the functions of attention. We outline several such networks that have been studied in normal and pathological states. These include networks for orienting to sensory stimuli, for maintaining the alert state, and for orchestrating volitional control. There is evidence that these networks have a certain degree of anatomical and functional independence, but that they also interact in many practical situations. Damage to each of these networks, irrespective of the source, produces distinctive neuropsychological deficits. We consider the links between the etiology of the injury and changes in cognition and behavior and examine the role of brain imaging in the study of rehabilitation.

Development of the functional visual field.

Andries Sanders' dissertation examined selective mechanisms in the functional visual field, and much of his work since has been concerned with the stages that underlie visual information processing particularly while making saccades. We argue that the study of orienting in the functional visual field is timely because it deals with the relation of covert attention shifts, eye movements and head movements to their underlying neurology. In our paper we develop a method to study learning of sequences at all ages from infants to adults. Our studies focus on how learning influences anticipatory eye movements. We examined the learning of unambiguous and context dependent sequences by 4-, 10-, and 18-month-old infants and undergraduates. We found clear learning of unambiguous sequences at 4 months, but learning of context dependent associations was found only in 18-month-olds and in adults. We hypothesize that the learning of unambiguous sequences by 4-month-olds reflects maturation of a basal ganglia-parietal circuit related to adult implicit learning, while the learning of context dependent sequences requires development of frontal structures underlying more general attentional abilities.

Correlation of brain rhythms between frontal and left temporal (Wernicke's) cortical areas during verbal thinking.

The aim of this study was to investigate an interaction between frontal and left temporo-parietal cortices in tasks requiring word association. A new method was used to examine averaged event-related potentials in different frequency bands by calculating correlation coefficients between wavelet curves in distant cortical areas. This method was applied to previous event-related potentials recordings which found successive activation of frontal and left posterior areas [1]. Correlated activity at 17 Hz was observed between frontal and left temporal (Wernicke's) areas prior to full activation of Wernicke's area.

Cognitive neuroscience: origins and promise.

Both Freud and Wundt had hoped to base psychology on an understanding of the neural basis of mental events. Their efforts were unsuccessful because the structure and function of the human brain was not available for empirical study at the physiological level. Over the last part of this century, there has been amazing growth and vitality in the field of human brain function. In this paper, we trace critical developments in the fields of cognitive psychology, neuropsychology, and brain imaging related to the development of cognitive neuroscience. Cognitive Neuroscience has established that the decomposition of mental events can be united with an understanding of the mental and emotional computations carried out by the human brain. Cognitive neuroscience has the capability of influencing psychology in diverse areas from how children develop to how adults age; from how humans learn to how we imagine; from volitional control to psychopathologies.

Cognitive neuroscience.

The last decade of the 20th century has seen the development of cognitive neuroscience as an effort to understand how the brain represents mental events. We review the areas of emotional and motor memory, vision, and higher mental processes as examples of this new understanding. Progress in all of these areas has been swift and impressive, but much needs to be done to reveal the mechanisms of cognition at the local circuit and molecular levels. This work will require new methods for controlling gene expression in higher animals and in studying the interactions between neurons at multiple levels.

Evaluation of attention process training and brain injury education in persons with acquired brain injury.

Fourteen patients with stable acquired brain injuries exhibiting attention and working memory deficits were given 10 weeks of attention process training (APT) and 10 weeks of brain injury education in a cross-over design. Structured interviews and neuropsychological tests were used prior to rehabilitation and after both treatments to determine the influence of the interventions on tasks of daily life and performance on attentional networks involving vigilance, orienting, and executive function. The overall results showed that most patients made improvements. Some of these gains were due to practice from repetitive administration of the tests. In addition, the type of intervention also influenced the results. The brain injury education seemed to be most effective in improving self-reports of psychosocial function. APT influenced self-reports of cognitive function and had a stronger influence on performance of executive attention tasks than was found with the brain injury education therapy. Vigilance and orienting networks showed little specific improvement due to therapy. However, vigilance level influenced the improvement with therapy on some tests of executive attention. We consider the implications of these results for future studies of the locus of attentional improvement and for the design of improved interventions.

Executive attention and metacognitive regulation.

Metacognition refers to any knowledge or cognitive process that monitors or controls cognition. We highlight similarities between metacognitive and executive control functions, and ask how these processes might be implemented in the human brain. A review of brain imaging studies reveals a circuitry of attentional networks involved in these control processes, with its source located in midfrontal areas. These areas are active during conflict resolution, error correction, and emotional regulation. A developmental approach to the organization of the anatomy involved in executive control provides an added perspective on how these mechanisms are influenced by maturation and learning, and how they relate to metacognitive activity.

Genetic and state variables of neurocognitive dysfunction in schizophrenia: a twin study.

To characterize the familiality of cognitive dysfunction in schizophrenia, we studied performance on three tasks (visuospatial attention; visuolinguistic conflict, arrow-word; and Wisconsin Card Sorting Test [WCST]) by monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia. The subject sample consisted of six MZ twin pairs, nine DZ twin pairs, and one MZ and one DZ nonschizophrenia cotwin of a patient with schizophrenia. There were two sources of cognitive dysfunction: a nonheritable, state component and a heritable, trait component. Deficits surfaced during the WCST in nonschizophrenia MZ cotwins; this impairment resolved following training in nonschizophrenia MZ cotwins, but not in the probands with schizophrenia, who performed abnormally in all tasks. The results suggest that nonheritable protective factors modulate the specific, plastic, and sometimes subtle neurocognitive deficits related to the schizophrenia genotype.

Computerized games to study the development of attention in childhood.

Children enjoy playing games. We can take advantage of this in the designs of computerized tasks that will engage their interest. These designs also serve to advance the study of chronometric measures, such as manual and saccadic reaction times and event related potentials, with young children. The goals of our method development are (1) to allow for comparable tasks across a wide variety of ages, (2) to make possible comparisons of child performance with data gathered in adult cognitive studies, and (3) to help to support inferences about the development of underlying mechanisms. We have designed a battery of computerized tasks in order to study the development of attention functions of alertness, orienting, and executive control during childhood. Our purpose is to describe each of these tasks in detail and present the results that have been obtained so far. The battery was tested using a sample of 5-year-old children as subjects.

Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention.

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Pathologies of brain attentional networks.

In the last decade, it has been possible to trace the areas of the human brain involved in a variety of cognitive and emotional processes by use of imaging technology. Brain networks that subserve attention have been described. It is now possible to use these networks as model systems for the exploration of symptoms arising from various forms of pathology. For example, we can use the orienting network to understand the effects of lesions that produce neglect of sensory information either by brain damage or by restricting transmitter input. Frontal attention networks may provide similar understanding of pathologies at higher levels of cognition. Evidence relating these networks to attention deficit and hyperactivity disorder (ADHD) is considered.

Development of brain networks for orienting to novelty.

Among the many contributions of I.P. Pavlov to the study of the higher nervous system was his exploration of the physical basis of attention. Pavlov's analysis of the orienting reflex (OR), together with the contributions of Y.N. Sokolov, demonstrated that attention could be studies by the objective methods of neurophysiology. Cognitive neuroscience has continued these effort by using neuroimaging to explore the anatomy and physiology of attention in the working human brain. It is now possible to show that the appearance of a novel visual event invokes multiple attentional networks that work in concert to orient to and process a novel object within a very brief exposure. In this paper, we describe cognitive studies of orienting to novelty in adults, examine the networks of neural areas involved in processing novel objects, and review the development in early life of these attentional networks. Orienting to novelty provides an excellent vehicle for examining how biology and experience shape the mechanisms of self-regulation and cognitive control.