Donna L. Dierker

Defining functional areas in individual human brains using resting functional connectivity MRI

The cerebral cortex is anatomically organized at many physical scales starting at the level of single neurons and extending up to functional systems. Current functional magnetic resonance imaging (fMRI) studies often focus at the level of areas, networks, and systems. Except in restricted domains, (e.g., topographically-organized sensory regions), it is difficult to determine area boundaries in the human brain using fMRI. The ability to delineate functional areas non-invasively would enhance the quality of many experimental analyses allowing more accurate across-subject comparisons of independently identified functional areas. Correlations in spontaneous BOLD activity, often referred to as resting state functional connectivity (rs-fcMRI), are especially promising as a way to accurately localize differences in patterns of activity across large expanses of cortex. In the current report, we applied a novel set of image analysis tools to explore the utility of rs-fcMRI for defining wide-ranging functional area boundaries. We find that rs-fcMRI patterns show sharp transitions in correlation patterns and that these putative areal boundaries can be reliably detected in individual subjects as well as in group data. Additionally, combining surface-based analysis techniques with image processing algorithms allows automated mapping of putative areal boundaries across large expanses of cortex without the need for prior information about a regions function or topography. Our approach reliably produces maps of bounded regions appropriate in size and number for putative functional areas. These findings will hopefully stimulate further methodological refinements and validations.

Surface-Based and Probabilistic Atlases of Primate Cerebral Cortex

Brain atlases play an increasingly important role in neuroimaging, as they are invaluable for analysis, visualization, and comparison of results across studies. For both humans and macaque monkeys, digital brain atlases of many varieties are in widespread use, each having its own strengths and limitations. For studies of cerebral cortex there is particular utility in hybrid atlases that capitalize on the complementary nature of surface and volume representations, are based on a population average rather than an individual brain, and include measures of variation as well as averages. Linking different brain atlases to one another and to online databases containing a growing body of neuroimaging data will enable powerful forms of data mining that accelerate discovery and improve research efficiency.

Similar patterns of cortical expansion during human development and evolution

The cerebral cortex of the human infant at term is complexly folded in a similar fashion to adult cortex but has only one third the total surface area. By comparing 12 healthy infants born at term with 12 healthy young adults, we demonstrate that postnatal cortical expansion is strikingly nonuniform: regions of lateral temporal, parietal, and frontal cortex expand nearly twice as much as other regions in the insular and medial occipital cortex. This differential postnatal expansion may reflect regional differences in the maturity of dendritic and synaptic architecture at birth and/or in the complexity of dendritic and synaptic architecture in adults. This expression may also be associated with differential sensitivity of cortical circuits to childhood experience and insults. By comparing human and macaque monkey cerebral cortex, we infer that the pattern of human evolutionary expansion is remarkably similar to the pattern of human postnatal expansion. To account for this correspondence, we hypothesize that it is beneficial for regions of recent evolutionary expansion to remain less mature at birth, perhaps to increase the influence of postnatal experience on the development of these regions or to focus prenatal resources on regions most important for early survival.

Cortical Folding Abnormalities in Autism Revealed by Surface-Based Morphometry

We tested for cortical shape abnormalities using surface-based morphometry across a range of autism spectrum disorders (7.5–18 years of age). We generated sulcal depth maps from structural magnetic resonance imaging data and compared typically developing controls to three autism spectrum disorder subgroups: low-functioning autism, high-functioning autism, and Aspergers syndrome. The low-functioning autism group had a prominent shape abnormality centered on the pars opercularis of the inferior frontal gyrus that was associated with a sulcal depth difference in the anterior insula and frontal operculum. The high-functioning autism group had bilateral shape abnormalities similar to the low-functioning group, but smaller in size and centered more posteriorly, in and near the parietal operculum and ventral postcentral gyrus. Individuals with Aspergers syndrome had bilateral abnormalities in the intraparietal sulcus that correlated with age, intelligence quotient, and Autism Diagnostic Interview-Revised social and repetitive behavior scores. Because of evidence suggesting age-related differences in the developmental time course of neural alterations in autism, separate analyses on children (7.5–12.5 years of age) and adolescents (12.75–18 years of age) were also carried out. All of the cortical shape abnormalities identified across all ages were more pronounced in the children. These findings are consistent with evidence of an altered trajectory of early brain development in autism, and they identify several regions that may have abnormal patterns of connectivity in individuals with autism.

A Surface-Based Analysis of Hemispheric Asymmetries and Folding of Cerebral Cortex in Term-Born Human Infants

We have established a population average surface-based atlas of human cerebral cortex at term gestation and used it to compare infant and adult cortical shape characteristics. Accurate cortical surface reconstructions for each hemisphere of 12 healthy term gestation infants were generated from structural magnetic resonance imaging data using a novel segmentation algorithm. Each surface was inflated, flattened, mapped to a standard spherical configuration, and registered to a target atlas sphere that reflected shape characteristics of all 24 contributing hemispheres using landmark constrained surface registration. Population average maps of sulcal depth, depth variability, three-dimensional positional variability, and hemispheric depth asymmetry were generated and compared with previously established maps of adult cortex. We found that cortical structure in term infants is similar to the adult in many respects, including the pattern of individual variability and the presence of statistically significant structural asymmetries in lateral temporal cortex, including the planum temporale and superior temporal sulcus. These results indicate that several features of cortical shape are minimally influenced by the postnatal environment.

Symmetry of Cortical Folding Abnormalities in Williams Syndrome Revealed by Surface-Based Analyses

We analyzed folding abnormalities in the cerebral cortex of subjects with Williams syndrome (WS), a genetically based developmental disorder, using surface-based analyses applied to structural magnetic resonance imaging data. Surfaces generated from each individual hemisphere were registered to a common atlas target (the PALS-B12 atlas). Maps of sulcal depth (distance from the cerebral hull) were combined across individuals to generate maps of average sulcal depth for WS and control subjects, along with depth-difference maps and t-statistic maps that accounted for within-group variability. Significant structural abnormalities were identified in 33 locations, arranged as 16 bilaterally symmetric pairs plus a lateral temporal region in the right hemisphere. Discrete WS folding abnormalities extended across a broad swath from dorsoposterior to ventroanterior regions of each hemisphere, in cortical areas associated with multiple sensory modalities as well as regions implicated in cognitive and emotional behavior. Hemispheric asymmetry in the temporal cortex is reduced in WS compared with control subjects. These findings provide insights regarding possible developmental mechanisms that give rise to folding abnormalities and to the spectrum of behavioral characteristics associated with WS.

Alterations in Brain Structure and Neurodevelopmental Outcome in Preterm Infants Hospitalized in Different Neonatal Intensive Care Unit Environments

OBJECTIVE To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at hospital discharge; and developmental outcomes at 2 years of age. STUDY DESIGN In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). RESULTS At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores (P = .02; β = -0.52 [CI -0.95, -0.10]). At age 2 years, infants from private rooms had lower language scores (P = .006; β = -8.3 [CI -14.2, -2.4]) and a trend toward lower motor scores (P = .02; β = -6.3 [CI -11.7, -0.99]), which persisted after adjustment for potential confounders. CONCLUSION These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.

Canonical genetic signatures of the adult human brain

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry.

Cortical Parcellations of the Macaque Monkey Analyzed on Surface-Based Atlases

Surface-based atlases provide a valuable way to analyze and visualize the functional organization of cerebral cortex. Surface-based registration (SBR) is a primary method for aligning individual hemispheres to a surface-based atlas. We used landmark-constrained SBR to register many published parcellation schemes to the macaque F99 surface-based atlas. This enables objective comparison of both similarities and differences across parcellations. Cortical areas in the macaque vary in surface area by more than 2 orders of magnitude. Based on a composite parcellation derived from 3 major sources, the total number of macaque neocortical and transitional cortical areas is estimated to be about 130-140 in each hemisphere.

Correspondences between retinotopic areas and myelin maps in human visual cortex.

We generated probabilistic area maps and maximum probability maps (MPMs) for a set of 18 retinotopic areas previously mapped in individual subjects (Georgieva et al., 2009 and Kolster et al., 2010) using four different inter-subject registration methods. The best results were obtained using a recently developed multimodal surface matching method. The best set of MPMs had relatively smooth borders between visual areas and group average area sizes that matched the typical size in individual subjects. Comparisons between retinotopic areas and maps of estimated cortical myelin content revealed the following correspondences: (i) areas V1, V2, and V3 are heavily myelinated; (ii) the MT cluster is heavily myelinated, with a peak near the MT/pMSTv border; (iii) a dorsal myelin density peak corresponds to area V3D; (iv) the phPIT cluster is lightly myelinated; and (v) myelin density differs across the four areas of the V3A complex. Comparison of the retinotopic MPM with cytoarchitectonic areas, including those previously mapped to the fs_LR cortical surface atlas, revealed a correspondence between areas V1–3 and hOc1–3, respectively, but little correspondence beyond V3. These results indicate that architectonic and retinotopic areal boundaries are in agreement in some regions, and that retinotopy provides a finer-grained parcellation in other regions. The atlas datasets from this analysis are freely available as a resource for other studies that will benefit from retinotopic and myelin density map landmarks in human visual cortex.