Avants, Brian B
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Publication Effect of Socioeconomic Status (SES) Disparity on Neural Development in Female African-American Infants at 1 Month(2016-11-01) Avants, Brian B; Betancourt, Laura; Farah, Martha J; Brodsky, Nancy L.; Wu, Jue; Ashtari, Manzar; Hurt, HallamThere is increasing interest in both the cumulative and long term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age two years. Less is known regarding the impact of SES on neural development in children before age two. This paper examines the effect of SES, indexed by income-to-needs (ITN) and maternal education, on cortical, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African American, female infants. At 44-46 post-conception weeks, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32-channel head coil). Images were segmented based on a locally-constructed template. Utilizing hierarchical linear regression, overall and component (maternal education and ITN) SES effects on MRI volumes were examined. In this cohort of healthy African American infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development.Publication Relation of Childhood Home Environment to Cortical Thickness in Late Adolescence: Specificity of Experience and Timing(2015-10-28) Avants, Brian B; Hackman, Daniel A; Betancourt, Laura; Lawson, Gwendolyn M; Farah, Martha J.; Hurt, HallamWhat are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing.Publication Multi-start Method with Prior Learning for Image Registration(2007-10-10) Song, Gang; Avants, Brian B; Gee, Jim C.We propose an efficient image registration strategy that is based on learned prior distributions of transformation parameters. These priors are used to constrain a finite- time multi-start optimization method. Motivation for this approach comes from the fact that standard affine brain image registration methods, especially those based on gradient descent optimization alone, are affected by the initial search position. While global optimization methods can resolve this problem, they are are often very time consuming. Our goal is to build an explicit prior model of the gap between a typical registration solution and the solution gained by a global optimization method. We use this learned prior model to restrict randomized search in the relevant parameter space surrounding the initial solution. Global optimization in this restricted parameter space provides, in finite time, results that are superior to both gradient descent and the general multi-start strategy. The performance of our method is illustrated on a data set of 67 elderly and neurodegenerative brains. Our novel learning strategy and the associated registration method are shown to outperform other approaches. Theoretical, synthetic and real-world examples illustrate this improvement.Publication Canine and Human Visual Cortex Intact and Responsive Despite Early Retinal Blindness from RPE65 Mutation(2007-06-26) Aguirre, Geoffrey K; Komáromy, András M; Cideciyan, Artur V; Brainard, David H; Aleman, Tomas S; Avants, Brian B; Gee, James C; Jacobson, Samuel G; Roman, Alejandro J; Korczykowski, Marc; Hauswirth, William W; Acland, Gregory MBackground RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA). Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA). Methods and Findings RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean ± standard deviation [SD] = 0.07% ± 0.06% and volume = 1.3 ± 0.6 cm3). Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% ± 0.06%) and volume (8.2 ± 0.8 cm3) of activation within the lateral gyrus (p < 0.005 for both). Cortical recovery occurred rapidly (within a month of treatment) and was persistent (as long as 2.5 y after treatment). Recovery was present even when treatment was provided as late as 1–4 y of age. Human RPE65-LCA patients (ages 18–23 y) were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 ± 0.5 mm) was within the normal range (3.2 ± 0.3 mm), and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005). Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 ± 1.2 cm3) compared to controls (29.7 ± 8.3 cm3, p < 0.001) when stimulated with lower intensity light. Unexpectedly, cortical response volume (41.2 ± 11.1 cm3) was comparable to normal (48.8 ± 3.1 cm3, p = 0.2) with higher intensity light stimulation. Conclusions Visual cortical responses dramatically improve after retinal gene therapy in the canine model of RPE65-LCA. Human RPE65-LCA patients have preserved visual pathway anatomy and detectable cortical activation despite limited visual experience. Taken together, the results support the potential for human visual benefit from retinal therapies currently being aimed at restoring vision to the congenitally blind with genetic retinal disease.