COMT genotype affects prefrontal white matter pathways in children and adolescents.

Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.

Does white matter matter? Spatio-temporal dynamics of task switching in aging.

Older adults often encounter difficulties in switching between tasks, perhaps because of age-related decreases in executive function. Executive function may largely depend on connections between brain areas-connections that may become structurally and functionally weaker in aging. Here we investigated functional and structural age-related changes in switching between a spatial and a verbal task. These tasks were chosen because they are expected to differentially use the two hemispheres. Brain measures included anatomical information about anterior corpus callosum size (CC; the major commissure linking the left and right hemisphere), and the event-related optical signal (EROS). Behavioral results indicated that older adults had greater task-switching difficulties, which, however, were largely restricted to switching to the spatial task and to individuals with smaller anterior CCs. The EROS data showed both general switching-related activity in the left middle frontal gyrus (with approximately 300-msec latency) and task-specific activity in the inferior frontal gyrus, lateralized to the left for the switch-to-verbal condition and to the right for the switch-to-spatial condition. This lateralization was most evident in younger adults. In older adults, activity in the switch-to-spatial condition was lateralized to the right hemisphere in individuals with large CC, and to the left in individuals with small CC. These data suggest that (a) task switching may involve both task-general and task-specific processes; and (b) white matter changes may underlie some of the age-related problems in switching. These effects are discussed in terms of the hypothesis that aging involves some degree of cortical disconnection, both functional and anatomical.

Neuroanatomical correlates of aging, cardiopulmonary fitness level, and education.

Fitness and education may protect against cognitive impairments in aging. They may also counteract age-related structural changes within the brain. Here we analyzed volumetric differences in cerebrospinal fluid and gray and white matter, along with neuropsychological data, in adults differing in age, fitness, and education. Cognitive performance was correlated with fitness and education. Voxel-based morphometry was used for a whole-brain analysis of structural magnetic resonance images. We found age-related losses in gray and white matter in medial-temporal, parietal, and frontal areas. As in previous work, fitness within the old correlated with preserved gray matter in the same areas. In contrast, higher education predicted preserved white matter in inferior frontal areas. These data suggest that fitness and education may both be predictive of preserved cognitive function in aging through separable effects on brain structure.