Assessing the molecular genetics of the development of executive attention in children: focus on genetic pathways related to the anterior cingulate cortex and dopamine

Abstract

It is well-known that children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Non-invasive neuroimaging in developing populations has revealed many neural correlates of behavior, particularly in the developing cingulate cortex and fronto-striatal circuits. These brain regions, themselves, undergo protracted molecular and cellular change in the first two decades of human development and, as such, are ideal regions of interest for cognitive-and imaging-genetic studies that seek to link processes at the biochemical and synaptic levels to brain activity and behavior. We review our research to-date that employs both adult and child-friendly versions of the Attention Network Task (ANT) in an effort to begin to describe the role of specific genes in the assembly of a functional attention system. Presently, we constrain our predictions for genetic association studies by focusing on the role of the anterior cingulate cortex (ACC) and of dopamine in the development of executive attention.

An Eight-week, Open-trial, Pilot Feasibility Study of Trigeminal Nerve Stimulation in Youth With Attention-deficit/Hyperactivity Disorder

“…Specifically, this result suggests that, over the course of TNS treatment, the speed of the inhibitory process became faster and more efficient. Prior neuroimaging studies using the ANT have found that successful performance on this task is associated with ACC activation [33]. The putative impact of TNS on the ACC seen in this study is consistent with earlier PET findings in adults with depression suggesting that TNS has functional benefits in specific brain regions [21].…”

Executive Function

“…In particular, impairments in EF are most pronounced among children with ADHD or ASD (Pennington and Ozonoff, 1996), two disorders that show substantial genetic influence (Kuntsi et al, 2004;Ronald et al, 2006). More direct evidence for strong genetic influences on early EF comes from studies that include genotyping (e.g., Fossella et al, 2002;Rueda et al, 2005), which demonstrate that children with the homozygous long allele for the DAT1 gene (associated with high effortful control and low extroversion) outperform those with the heterozygous (long/ short) allele on EF tests of conflict resolution (for a recent review of molecular genetic studies of EF in children, see Brocki et al, 2009). More direct evidence for strong genetic influences on early EF comes from studies that include genotyping (e.g., Fossella et al, 2002;Rueda et al, 2005), which demonstrate that children with the homozygous long allele for the DAT1 gene (associated with high effortful control and low extroversion) outperform those with the heterozygous (long/ short) allele on EF tests of conflict resolution (for a recent review of molecular genetic studies of EF in children, see Brocki et al, 2009).…”

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

“…The flankers point either in the same direction as the target arrow (congruent) or in the opposite direction (incongruent) and a subtraction of RTs of congruent from incongruent target trials provides a measure of conflict resolution that assesses the efficiency of the executive attention network. Our current data were obtained from a collection of 110 healthy children somewhat evenly distributed in gender and ages 5–13 years old who performed the task while under adult supervision 163 . A view of both the distribution of raw and of normalized (conflict RT/overall RT) shows that children experience a RT cost of about 90 ms related to the resolution of stimulus–response conflict and that there is little change in the efficiency of conflict resolution as children mature beyond this age range.…”