White matter correlates of cognitive inhibition during development: A diffusion tensor imaging study
Introduction
The transition from childhood to adolescence is marked by significant reorganization of the brain, in concert with extensive emotional, cognitive and behavioral development, allowing children to act toward goals, focus their attention, control impulses, flexibly employ strategies, and self-monitor their behavior (Levin et al., 1991, Davidson et al., 2006, Bunge and Wright, 2007). Inhibition, one’s ability to withhold an automatic response or to resist enticing behaviors, and cognitive flexibility, the ability to adapt behavior or thought processes to meet changing environmental demands, are two key cognitive functions that vary considerably among individuals and undergo significant change across the lifespan. Both improve with age during childhood, stabilize in mid adolescence to adulthood (Williams et al., 1999, Davidson et al., 2006), and are among the earliest executive functions to deteriorate in dementia (Amieva et al., 2004, Traykov et al., 2007). Deficits of inhibition are associated with high-risk behaviors, impulsivity, addiction, conduct problems, and affective problems, and are characteristic of numerous developmental and psychiatric disorders (Roussy and Toupin, 2000, Herba et al., 2006, van Deurzen et al., 2012). Even in healthy populations, performance on inhibition tasks has been shown to predict behavior problems, delinquency, and future substance use in longitudinal studies (Tremblay et al., 1994, Kerr et al., 1997, Mahmood et al., 2013).
Functional magnetic resonance imaging (MRI) studies of response inhibition in children and adults suggest that maturation of dorsolateral and orbitofrontal, anterior cingulate cortices (Casey et al., 1997, Rubia et al., 2006, Aron et al., 2007), parietal, and striatal areas (Rubia et al., 2006) is associated with task performance. Likewise, structural MRI studies have also identified relationships between performance on inhibition tasks and structural gray matter parameters, such as surface area of cingulate cortex (Fjell et al., 2012), and cortical thickness of occipital and parietal regions (Tamnes et al., 2010a) in children, though the role of underlying white matter is less understood.
Several diffusion tensor imaging (DTI) studies have linked white matter structure with measures of inhibition in healthy subjects. Better inhibitory performance has been associated with higher white matter fractional anisotropy (FA) of frontal areas (Forstmann et al., 2008) and frontal-basal ganglia tracts (King et al., 2012) using Simon and stop-signal tasks, respectively, in healthy adults. Similarly in children, better inhibition has been correlated with higher FA and/or lower perpendicular diffusivity in frontostriatal tracts (Liston et al., 2006 using a go-no-go task), right inferior frontal gyrus and right pre-supplemental motor area (Madsen et al., 2010 using a stop-signal task), posterior projections of the corpus callosum (CC) (Fjell et al., 2012 using a flanker task), posterior thalamic radiation and cerebral peduncle (Chaddock-Heyman et al., 2013, using a flanker task) and the right anterior corona radiata (Seghete et al., 2013 using a Stroop task). Most of these studies found that associations between FA and inhibitory performance were independent of age, albeit across relatively narrow spans of adolescence (Liston et al., 2006, Madsen et al., 2010, Seghete et al., 2013), though the strength of correlation between FA and performance has also been shown to vary with age from 5 to 21 years (Fjell et al., 2012). Likewise, increased FA of the anterior corona radiata has been associated with better task switching in children (10–11 years) but not adolescents (12–16 years) (Seghete et al., 2013) suggesting a complex relationship between white matter maturation and cognitive control. Differences between boys and girls in the locations of white matter FA-inhibition relationships (Silveri et al., 2006) suggest that gender may also mediate aspects of this relationship.
White matter FA has also been associated with inhibition performance in clinical pediatric populations, albeit with variable regional findings. Higher FA of prefrontal white matter areas has been shown to correlate with better inhibitory performance on a go/no-go task in children with attention deficit hyperactivity disorder (ADHD), and their unaffected parents (Casey et al., 2007). Likewise, a study of children with traumatic brain injuries found that higher FA of the splenium correlated with increased processing speed and better interference resolution on a flanker task (Wilde et al., 2006). Conversely, a study of adolescents with prenatal cocaine exposure found that lower FA of the right cingulum correlated with better performance on a Stroop task (Lebel et al., 2013), though an opposite relationship was found in the control group.
Although informative, previous studies have used a variety of image analysis methods and cognitive measures, with few studies using normed clinical tests of inhibition and cognitive flexibility. The purpose of this study is to examine the correlates of white matter microstructure indices from DTI (i.e. FA) with inhibition and cognitive flexibility in 49 healthy 5–16-year old children and adolescents using the NEPSY-II Inhibition test, a commonly used neuropsychological assessment tool. An understanding of these brain behavior relationships in childhood may provide a baseline to identify deviations in adolescent psychopathology and across the lifespan.
Section snippets
Participants
Participants were 49 children and adolescents, 5–16 years of age (mean = 11.5 ± 2.8 years, 20 females, 29 males), recruited through advertising in the community and flyers sent home in schools. Participants were newly recruited and not included in any of our previous MRI studies of brain development. Children were screened for neurological, psychiatric or developmental disorders, head injuries, and contraindications to MRI. Written informed consent was obtained from all participants’ parent/legal
Cognitive scores
Children performed average to above average on WRIT IQ (mean 111 ± 13) with no differences between genders and no significant effect of age (Table 1). NEPSY-II Naming, Inhibition, and Switching scaled scores were not different from population norms, and did not change with age or differ by gender (Table 1). Linear regression revealed significant decreases in raw time and errors for all three conditions (Naming, Inhibition and Switching), but no effect of gender or age-by-gender (Fig. 1). The four
Discussion
This study demonstrates associations between DTI measures of white matter and cognitive inhibition in a sample of 49 healthy children and adolescents. Voxel-based analysis revealed several clusters in frontal and posterior white matter regions where worse inhibition performance correlated with higher FA, while also producing clusters in posterior and brainstem regions where better cognitive flexibility was associated with higher FA, suggesting a dichotomous relationship between FA and these two
Conclusion
Several associations between a white matter DTI-derived parameter (FA) and performance using a standardized measure of inhibition and cognitive flexibility are reported in 49 healthy children and adolescents. Tractography supports a role of the frontal projections of the CC in the emergence and variability of this important executive function.
Acknowledgments
This research was funded by the Canadian Institutes for Health Research (CIHR); salary support was provided by Alberta Innovates- Health Solutions (AIHS) (C.B. and S.T.) and the Women’s and Children’s Health Research Institute (WCHRI) (S.T.). We would like to thank Lauren Baugh for her help with cognitive testing, and the parents and children who participated in this study.
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