Suzanne E. Welcome

Mapping cortical change across the human life span

We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

Longitudinal Mapping of Cortical Thickness and Brain Growth in Normal Children

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of ∼0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Brocas area) and bilateral posterior perisylvian (Wernickes area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.

Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder

BACKGROUND Results of structural brain imaging studies of patients with attention-deficit hyperactivity disorder have shown subtle reductions in total brain volume and in volumes of the right frontal lobe and caudate nucleus. Although various conventional volumetric and voxel-based methods of image analysis have been used in these studies, regional brain size and grey-matter abnormalities have not yet been mapped over the entire cortical surface in patients with this disorder. We aimed to map these features in patients with attention-deficit hyperactivity disorder. METHODS We used high-resolution MRI and surface-based, computational image analytic techniques to map regional brain size and grey-matter abnormalities at the cortical surface in a group of 27 children and adolescents with attention-deficit hyperactivity disorder and 46 controls, who were group-matched by age and sex. FINDINGS Abnormal morphology was noted in the frontal cortices of patients with attention-deficit hyperactivity disorder, with reduced regional brain size localised mainly to inferior portions of dorsal prefrontal cortices bilaterally. Brain size was also reduced in anterior temporal cortices bilaterally. Prominent increases in grey matter were recorded in large portions of the posterior temporal and inferior parietal cortices bilaterally. INTERPRETATION The frontal, temporal, and parietal regions are heteromodal association cortices that constitute a distributed neural system, which subserves attention and behavioural inhibition. We have identified region-specific anatomical abnormalities in cortical components of attentional systems, which may help better account for the symptoms of attention-deficit hyperactivity disorder.

Size Matters: Cerebral Volume Influences Sex Differences in Neuroanatomy

Biological and behavioral differences between the sexes range from obvious to subtle or nonexistent. Neuroanatomical differences are particularly controversial, perhaps due to the implication that they might account for behavioral differences. In this sample of 200 men and women, large effect sizes (Cohens d > 0.8) were found for sex differences in total cerebral gray and white matter, cerebellum, and gray matter proportion (women had a higher proportion of gray matter). The only one of these sex differences that survived adjustment for the effect of cerebral volume was gray matter proportion. Individual differences in cerebral volume accounted for 21% of the difference in gray matter proportion, while sex accounted for an additional 4%. The relative size of the corpus callosum was 5% larger in women, but this difference was completely explained by a negative relationship between relative callosal size and cerebral volume. In agreement with Jancke et al., individuals with higher cerebral volume tended to have smaller corpora callosa. There were few sex differences in the size of structures in Brocas and Wernickes area. We conclude that individual differences in brain volume, in both men and women, account for apparent sex differences in relative size.

Mapping Cortical Gray Matter Asymmetry Patterns in Adolescents with Heavy Prenatal Alcohol Exposure

Here we report on detailed three-dimensional quantitative maps of brain surface and gray matter density asymmetry patterns during normal adolescent development and show how these anatomical features of the brain are disrupted as a result of prenatal exposure to large quantities of alcohol. We studied two independent samples of normally developing children, adolescents, and young adults, totaling 83 subjects from two different research groups, and compared them to 21 individuals with heavy prenatal alcohol exposure. Surface-based image analysis techniques allowed us to match cortical anatomy across subjects and between hemispheres based on manually delineated sulcal landmarks. Quantitative maps of brain surface asymmetry reveal prominent peri-Sylvian hemispheric differences in which the superior temporal and inferior parietal cortices are shifted backward in the left relative to the right hemisphere in both normal and alcohol-exposed subjects. Cortical surface gray matter asymmetry, mapped here in adolescent populations, is most prominent in the posterior inferior temporal lobes (right greater than left), and this effect does not differ between groups of normally developing children, adolescents, or young adults. Alcohol-exposed individuals show a significant reduction in this asymmetry, whether studied with surface-based or more traditional volumetric region of interest analyses. This region of cortex, near the junction of Brodmanns areas 21, 22, and 37, primarily subserves language functions that are known to be impaired on average in the alcohol-exposed subjects. Our findings elucidate regional patterns of brain surface and gray matter asymmetry during normal development and may contribute to a more comprehensive understanding of the neural substrates of cognitive dysfunction after heavy prenatal alcohol exposure.

Mapping brain size and cortical gray matter changes in elderly depression

BACKGROUND In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.

A Large-Scale Investigation of Lateralization in Cortical Anatomy and Word Reading: Are There Sex Differences?

The authors report findings of a large-scale, multitask investigation of sex differences in both structural asymmetries and lateralization of word reading. Two hundred participants were tested in eight divided visual field lexical tasks, and each received a structural magnetic resonance imaging scan. The authors examined whether there was evidence for sex differences in overall measures of neuroanatomical and behavioral lateralization, in specific language tasks and brain regions, and in variation in asymmetry within and across tasks and brain regions. There was very little evidence for sex differences on any behavioral measure. The few indications of sex differences in the current report accounted for 2% or less of the individual variation in asymmetry and could not be replicated in independent subsamples. No sex differences were observed in the asymmetry of structures in Brocas and Wernickes areas such as pars triangularis, pars opercularis, the planum temporale, planum parietale, or Heschls gyrus. There were also no sex differences in the variability of neuroanatomical asymmetries within or between brain regions. However, a significant relationship between planum temporale and behavioral asymmetry was restricted to men.

Behavioral correlates of corpus callosum size: Anatomical/behavioral relationships vary across sex/handedness groups

There are substantial individual differences in the size and shape of the corpus callosum and such differences are thought to relate to behavioral lateralization. We report findings from a large scale investigation of relationships between brain anatomy and behavioral asymmetry on a battery of visual word recognition tasks. A sample of 200 individuals was divided into groups on the basis of sex and consistency of handedness. We investigated differences between sex/handedness groups in callosal area and relationships between callosal area and behavioral predictors. Sex/handedness groups did not show systematic differences in callosal area or behavioral asymmetry. However, the groups differed in the relationships between area of the corpus callosum and behavioral asymmetry. Among consistent-handed males, callosal area was negatively related to behavioral laterality. Among mixed-handed males and consistent-handed females, behavioral laterality was not predictive of callosal area. The most robust relationship was observed in mixed-handed females, in whom behavioral asymmetry was positively related to callosal area. Our study demonstrates the importance of considering brain/behavior relationships within sub-populations, as relationships between behavioral asymmetry and callosal anatomy varied across subject groups.

Does degree of asymmetry relate to performance? An investigation of word recognition and reading in consistent and mixed handers

Is it advantageous to be strongly lateralized? The current study investigated this question by examining the relationship between visual field asymmetries for lexical tasks and reading performance in a sample of 200 young adults. Larger visual field asymmetries were associated with better reading performance, but this relationship was obtained primarily in those with strong and consistent hand preferences. Among mixed handers, variation in visual field asymmetry accounted for little or no variance in reading skill. In addition, correlations between visual field asymmetry and reading performance were observed for word recognition tasks, but not for tasks requiring controlled semantic retrieval. The results are consistent with the idea that consistent and mixed handers may represent differing neurobehavioral populations. Because greater lateralization was associated with better reading skill only for consistent handers, reduced behavioral asymmetry cannot be assumed to be a risk factor for reading dysfunction in the population as a whole.

Paracingulate asymmetry in anterior and midcingulate cortex: sex differences and the effect of measurement technique

Many structural brain asymmetries accompany left hemisphere language dominance. For example, the cingulate sulcus is larger in the medial cortex of the right hemisphere, while the more dorsal paracingulate sulcus is larger on the left. The functional significance of these asymmetries is unknown because fMRI studies rarely attempt to localize activation to specific sulci, possibly due to difficulties in consistent sulcal identification. In medial cortex, for example, there are many regions of partial sulcal overlap where MRI images do not provide sufficient information to unambiguously distinguish a paracingulate sulcus from a displaced anterior cingulate segment. As large samples of postmortem material are rarely available for cytoarchitectural studies of sulcal variation, we have investigated the effect of variation in boundary and sulcal definition on paracingulate asymmetry in the MRI scans of 200 healthy adults (100 men, 100 women). Although women displayed a reliable asymmetry in the size of the paracingulate sulcus, regardless of boundary definition or technique, asymmetry was greatest when (1) the measurement was limited to the midcingulate region between the genu and the anterior commissure; and (2) the more dorsal of two overlapping sulci was always classified as a paracingulate sulcus (rather than as a displaced cingulate segment). The fact that paracingulate asymmetry is maximal in the midcingulate region suggests that this region may play a particular role in hemispheric specialization for language. Future work should investigate the structural and functional correlates of sulcal variation in this region.