Jason D. Yeatman

Tract Profiles of White Matter Properties: Automating Fiber-Tract Quantification

Tractography based on diffusion weighted imaging (DWI) data is a method for identifying the major white matter fascicles (tracts) in the living human brain. The health of these tracts is an important factor underlying many cognitive and neurological disorders. In vivo, tissue properties may vary systematically along each tract for several reasons: different populations of axons enter and exit the tract, and disease can strike at local positions within the tract. Hence quantifying and understanding diffusion measures along each fiber tract (Tract Profile) may reveal new insights into white matter development, function, and disease that are not obvious from mean measures of that tract. We demonstrate several novel findings related to Tract Profiles in the brains of typically developing children and children at risk for white matter injury secondary to preterm birth. First, fractional anisotropy (FA) values vary substantially within a tract but the Tract FA Profile is consistent across subjects. Thus, Tract Profiles contain far more information than mean diffusion measures. Second, developmental changes in FA occur at specific positions within the Tract Profile, rather than along the entire tract. Third, Tract Profiles can be used to compare white matter properties of individual patients to standardized Tract Profiles of a healthy population to elucidate unique features of that patients clinical condition. Fourth, Tract Profiles can be used to evaluate the association between white matter properties and behavioral outcomes. Specifically, in the preterm group reading ability is positively correlated with FA measured at specific locations on the left arcuate and left superior longitudinal fasciculus and the magnitude of the correlation varies significantly along the Tract Profiles. We introduce open source software for automated fiber-tract quantification (AFQ) that measures Tract Profiles of MRI parameters for 18 white matter tracts. With further validation, AFQ Tract Profiles have potential for informing clinical management and decision-making.

Anatomical properties of the arcuate fasciculus predict phonological and reading skills in children

For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.

Development of white matter and reading skills

White matter tissue properties are highly correlated with reading proficiency; we would like to have a model that relates the dynamics of an individual’s white matter development to their acquisition of skilled reading. The development of cerebral white matter involves multiple biological processes, and the balance between these processes differs between individuals. Cross-sectional measures of white matter mask the interplay between these processes and their connection to an individual’s cognitive development. Hence, we performed a longitudinal study to measure white-matter development (diffusion-weighted imaging) and reading development (behavioral testing) in individual children (age 7–15 y). The pattern of white-matter development differed significantly among children. In the left arcuate and left inferior longitudinal fasciculus, children with above-average reading skills initially had low fractional anisotropy (FA) that increased over the 3-y period, whereas children with below-average reading skills had higher initial FA that declined over time. We describe a dual-process model of white matter development comprising biological processes with opposing effects on FA, such as axonal myelination and pruning, to explain the pattern of results.

Diffusion Tensor Imaging: A Review for Pediatric Researchers and Clinicians

Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that allows for the visualization and characterization of the white matter tracts of the brain in vivo. DTI does not assess white matter directly. Rather, it capitalizes on the fact that diffusion is isotropic (equal in all directions) in cerebral spinal fluid and cell bodies but anisotropic (greater in one direction than the other directions) in axons that comprise white matter. It provides quantitative information about the degree and direction of water diffusion within individual units of volume within the magnetic resonance image, and by inference, about the integrity of white matter. Measures from DTI can be applied throughout the brain or to regions of interest. Fiber tract reconstruction, or tractography, creates continuous 3-dimensional tracts by sequentially piecing together estimates of fiber orientation from the direction of diffusion within individual volume units. DTI has increased our understanding of white matter structure and function. DTI shows nonlinear growth of white matter tracts from childhood to adulthood. Delayed maturation of the white matter in the frontal lobes may explain the continued growth of cognitive control into adulthood. Relative to good readers, adults and children who are poor readers have evidence of white matter differences in a specific region of the temporo-parietal lobe, implicating differences in connections among brain regions as a factor in reading disorder. Measures from DTI changed in poor readers who improved their reading skills after intense remediation. DTI documents injury to white matter tracts after prematurity. Measures indicative of white matter injury are associated with motor and cognitive impairment in children born prematurely. Further research on DTI is necessary before it can become a routine clinical procedure.

Anatomy of the visual word form area: Adjacent cortical circuits and long-range white matter connections

Circuitry in ventral occipital-temporal cortex is essential for seeing words. We analyze the circuitry within a specific ventral-occipital region, the visual word form area (VWFA). The VWFA is immediately adjacent to the retinotopically organized VO-1 and VO-2 visual field maps and lies medial and inferior to visual field maps within motion selective human cortex. Three distinct white matter fascicles pass within close proximity to the VWFA: (1) the inferior longitudinal fasciculus, (2) the inferior frontal occipital fasciculus, and (3) the vertical occipital fasciculus. The vertical occipital fasciculus terminates in or adjacent to the functionally defined VWFA voxels in every individual. The vertical occipital fasciculus projects dorsally to language and reading related cortex. The combination of functional responses from cortex and anatomical measures in the white matter provides an overview of how the written word is encoded and communicated along the ventral occipital-temporal circuitry for seeing words.

Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging

Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

Evaluation and statistical inference for human connectomes

Diffusion-weighted imaging coupled with tractography is currently the only method for in vivo mapping of human white-matter fascicles. Tractography takes diffusion measurements as input and produces the connectome, a large collection of white-matter fascicles, as output. We introduce a method to evaluate the evidence supporting connectomes. Linear fascicle evaluation (LiFE) takes any connectome as input and predicts diffusion measurements as output, using the difference between the measured and predicted diffusion signals to quantify the prediction error. We use the prediction error to evaluate the evidence that supports the properties of the connectome, to compare tractography algorithms and to test hypotheses about tracts and connections.

The vertical occipital fasciculus: A century of controversy resolved by in vivo measurements

Significance The vertical occipital fasciculus (VOF) is a major white-matter fascicle connecting dorsal and ventral visual cortex. Few vision scientists or cognitive neuroscientists are aware of the VOFs existence. The scarcity of papers on this important pathway stems from the contentious history surrounding its discovery by Wernicke in 1881. We review the conflict surrounding the classic, postmortem, VOF measurements, and we introduce modern, in vivo methods to precisely characterize the VOFs cortical terminations and unique tissue properties. The new VOF measurements provide insight into the communication between ventral stream regions involved in form perception and dorsal stream regions involved in eye movements and attention. The vertical occipital fasciculus (VOF) is the only major fiber bundle connecting dorsolateral and ventrolateral visual cortex. Only a handful of studies have examined the anatomy of the VOF or its role in cognition in the living human brain. Here, we trace the contentious history of the VOF, beginning with its original discovery in monkey by Wernicke (1881) and in human by Obersteiner (1888), to its disappearance from the literature, and recent reemergence a century later. We introduce an algorithm to identify the VOF in vivo using diffusion-weighted imaging and tractography, and show that the VOF can be found in every hemisphere (n = 74). Quantitative T1 measurements demonstrate that tissue properties, such as myelination, in the VOF differ from neighboring white-matter tracts. The terminations of the VOF are in consistent positions relative to cortical folding patterns in the dorsal and ventral visual streams. Recent findings demonstrate that these same anatomical locations also mark cytoarchitectonic and functional transitions in dorsal and ventral visual cortex. We conclude that the VOF is likely to serve a unique role in the communication of signals between regions on the ventral surface that are important for the perception of visual categories (e.g., words, faces, bodies, etc.) and regions on the dorsal surface involved in the control of eye movements, attention, and motion perception.

Lifespan maturation and degeneration of human brain white matter

Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative MRI measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7–85). The amount of R1 change during development differs between white matter fascicles, but in each fascicle the rate of development and decline are mirror symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white matter tissue properties over the lifespan.

Learning to See Words

Skilled reading requires recognizing written words rapidly; functional neuroimaging research has clarified how the written word initiates a series of responses in visual cortex. These responses are communicated to circuits in ventral occipitotemporal (VOT) cortex that learn to identify words rapidly. Structural neuroimaging has further clarified aspects of the white matter pathways that communicate reading signals between VOT and language systems. We review this circuitry, its development, and its deficiencies in poor readers. This review emphasizes data that measure the cortical responses and white matter pathways in individual subjects rather than group differences. Such methods have the potential to clarify why a child has difficulty learning to read and to offer guidance about the interventions that may be useful for that child.