A gene-brain-cognition pathway: prefrontal activity mediates the effect of COMT on cognitive control and IQ.

A core thesis of cognitive neurogenetic research is that genetic effects on cognitive ability are mediated by specific neural functions, however, demonstrating neural mediation has proved elusive. Pairwise relationships between genetic variation and brain function have yielded heterogeneous findings to date. This heterogeneity indicates that a multiple mediator modeling approach may be useful to account for complex relationships involving function at multiple brain regions.

Neurogenetics and pharmacology of learning, motivation, and cognition.

Many of the individual differences in cognition, motivation, and learning-and the disruption of these processes in neurological conditions-are influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies.

Genetics as a tool for the dissociation of mental operations over the course of development.

In recent years it has become possible to differentiate separable aspects of attention and to characterize the anatomical structure and dynamic states of their underlying networks. When individual differences in the structure and dynamics of these networks are used as dependent measures in associations with individual genetic variation, it becomes possible to assign cellular and molecular changes that occur over the course of normal development to specific aspects of network structure and function. In this way, a more granular understanding of the physiology of neural networks can be obtained.

Using genetic data in cognitive neuroscience: from growing pains to genuine insights.

Research that combines genetic and cognitive neuroscience data aims to elucidate the mechanisms that underlie human behaviour and experience by way of 'intermediate phenotypes': variations in brain function. Using neuroimaging and other methods, this approach is poised to make the transition from health-focused investigations to inquiries into cognitive, affective and social functions, including ones that do not readily lend themselves to animal models. The growing pains of this emerging field are evident, yet there are also reasons for a measured optimism.

Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation.

Objective: The dopamine transporter (DAT1) gene has been implicated in attention-deficit/hyperactivity disorder (ADHD), although the mechanism by which it exerts its effects remains unknown. The polymorphism associated with ADHD has been shown to affect expression of the transporter in vitro and in vivo. Dopamine transporters are predominantly expressed in the striatum, but also in the cerebellar vermis.

The functional integration of the anterior cingulate cortex during conflict processing.

Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively.

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.

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.

Specificity of the effect of a nicotinic receptor polymorphism on individual differences in visuospatial attention.

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention.

Maternal separation suppresses TGF alpha mRNA expression in the prefrontal cortex of male and female neonatal C57BL/6 mice.

Male C57BL/6 mice that undergo maternal separation (MS) early in life demonstrate higher levels of anxiety upon reaching adulthood compared to normally reared offspring. This study reports that neonatal males and females that undergo MS have reduced mRNA levels of transforming growth factor-alpha (TGF alpha) in the prefrontal cortex, an area of the brain implicated in emotionality, compared to normally reared animals. TGF alpha expression was unaffected by MS in the hippocampus.

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.

Synaptogenesis and heritable aspects of executive attention.

In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development.

Identification of quantitative trait Loci that affect aggressive behavior in mice.

Despite the previous development of single-gene knock-out mice that exhibit alterations in aggressive behavior, very little progress has been made toward identifying the natural gene variants (alleles) that contribute to individual or strain differences in aggression. Whereas most inbred mouse strains show an intermediate level of inter-male aggression in the resident-intruder or dangler behavioral tests, NZB/B1NJ mice are extremely aggressive and A/J mice are extremely unaggressive. We took advantage of the large phenotypic difference between these strains and used an outcross-backcross breeding protocol and a genome-wide scan to identify aggression quantitative trait loci (QTLs) on distal chromosome 10 (Aggr1; p = 6 x 10(-7)) and proximal chromosome X (Aggr2; p = 2.