White matter microstructure and atypical visual orienting in 7 month-olds at risk for autism

pre-printObjective: The authors sought to determine whether specific patterns of oculo-motor functioning and visual orientingcharacterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors. Method:Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low- risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal path-ways and the splenium and genu of the corpus callosum. Results: Visual orienting latencies were longer in 7-month-old infants who ex-pressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD. Conclusions: Flexiblyandef ficientlyorienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis

Contaminant biotransport by Pacific salmon to Lake Michigan tributaries

The Great Lakes are ideal systems for evaluating the synergistic components of environmental change, such as exotic species introductions and legacy pollutants. Introduced Pacific Salmon (Oncorhynchus spp.) represent an intersection of these drivers because they are non-native species of economic importance that bioaccumulate contaminants during the open water phase of their life cycle. Furthermore, Pacific salmon can deliver a significant pulse of contaminated tissue to tributaries during spawning and subsequent death. Thus, salmon represent a key pathway by which contaminants accumulated in Lake Michigan are transported inland to tributaries that otherwise lack point source pollution. Our research has revealed that salmon exhibit basin-specific persistent organic pollutant (POP) and mercury (Hg) concentrations reflecting pollutant inputs from both current and historic sources. Overall, Lake Michigan salmon were more contaminated with POPs and Hg than conspecifics from Lakes Huron or Superior. Consequently, Lake Michigan salmon pose a higher risk and magnitude of contaminant biotransport and transfer. Resident stream fish (e.g., brook trout) sampled from salmon spawning reaches had higher pollutant concentrations than fish sampled from upstream reaches lacking salmon, but the extent of fish contamination varied among lake basins and streams. In general, Lake Michigan tributaries were the most impacted, suggesting a direct relationship between the extent of salmon-derived contaminant inputs and resident fish contaminant levels. Within and among lake basins, contaminant biotransport by salmon is context dependent and likely reflects a suite of ecological characteristics such as species identity and trophic position, dynamics of the salmon run, watershed land-use, and instream geomorphology such as sediment size. We suggest that future management of salmon-mediated contaminant biotransport to stream communities in the Great Lakes basin should consider biological, chemical, and physical factors that constitute the environmental context

Frontolimbic neural circuitry at 6 months predicts individual differences in joint attention at 9 months

Elucidating the neural basis of joint attention in infancy promises to yield important insights into the development of language and social cognition, and directly informs developmental models of autism. We describe a new method for evaluating responding to joint attention performance in infancy that highlights the 9- to 10-month period as a time interval of maximal individual differences. We then demonstrate that fractional anisotropy in the right uncinate fasciculus, a white matter fiber bundle connecting the amygdala to the ventral-medial prefrontal cortex and anterior temporal pole, measured in 6-month-olds predicts individual differences in responding to joint attention at 9 months of age. The white matter microstructure of the right uncinate was not related to receptive language ability at 9 months. These findings suggest that the development of core nonverbal social communication skills in infancy is largely supported by preceding developments within right lateralized frontotemporal brain systems

Splenium development and early spoken language in human infants

The association between developmental trajectories of language-related white matter fiber pathways from 6 to 24 months of age and individual differences in language production at 24 months of age was investigated. The splenium of the corpus callosum, a fiber pathway projecting through the posterior hub of the default mode network to occipital visual areas, was examined as well as pathways implicated in language function in the mature brain, including the arcuate fasciculi, uncinate fasciculi, and inferior longitudinal fasciculi. The hypothesis that the development of neural circuitry supporting domain-general orienting skills would relate to later language performance was tested in a large sample of typically developing infants. The present study included 77 infants with diffusion weighted MRI scans at 6, 12 and 24 months and language assessment at 24 months. The rate of change in splenium development varied significantly as a function of language production, such that children with greater change in fractional anisotropy (FA) from 6 to 24 months produced more words at 24 months. Contrary to findings from older children and adults, significant associations between language production and FA in the arcuate, uncinate, or left inferior longitudinal fasciculi were not observed. The current study highlights the importance of tracing brain development trajectories from infancy to fully elucidate emerging brain-behavior associations while also emphasizing the role of the splenium as a key node in the structural network that supports the acquisition of spoken language

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area

PDEs for tensor image processing

Methods based on partial differential equations (PDEs) belong to those image processing techniques that can be extended in a particularly elegant way to tensor fields. In this survey paper the most important PDEs for discontinuity-preserving denoising of tensor fields are reviewed such that the underlying design principles becomes evident. We consider isotropic and anisotropic diffusion filters and their corresponding variational methods, mean curvature motion, and selfsnakes. These filters preserve positive semidefiniteness of any positive semidefinite initial tensor field. Finally we discuss geodesic active contours for segmenting tensor fields. Experiments are presented that illustrate the behaviour of all these methods

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6–24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females

Contaminant biotransport by Pacific Salmon in Lake Michigan: analysis of salmon and stream-resident fish in Great Lakes tributaries

Pacific salmon (Oncorhynchus spp.) can deliver a significant pulse of biomass, including its bioaccumulated contaminants, to tributaries during spawning runs. Thus, salmon transport contaminants accumulated in the Great Lakes (e.g., persistent organic pollutants [POPs], total mercury [THg]) to tributaries that otherwise lack point source pollution. We used a combination of observational surveys, experimental manipulations, and modeling, to (1) assess the extent of salmon-mediated biotransport across the upper Great Lakes; (2) determine pathways by which stream fish become contaminated by salmon; and (3) forecast areas at significant risk from salmon biotransport. Resident stream fish (e.g., brook trout Salvelinus fontinalis) in salmon spawning reaches had higher POP concentrations than fish in upstream reaches lacking salmon, but the extent of contamination varied among lake basins and streams. In contrast, THg concentrations in the same fish did not differ between reaches with and without salmon spawners but exhibited considerable among-site variability. In general, resident fish in Lake Michigan tributaries were the most contaminated by POPs, suggesting a direct relationship between salmon-derived contaminant inputs and resident fish contaminant levels. Experimental exposure to salmon carcasses and eggs for 50 days increased brook trout POP concentrations by 50 times. Eggs are elevated in POPs but depleted in THg compared to whole salmon, suggesting that resident fish contaminant levels reflect direct consumption of eggs rather than indirect food web pathways. Our model suggests that salmon-mediated bioaccumulation is primarily influenced by the size and duration of salmon runs, and secondarily by factors including individual consumption rates, temperature regime, and background pollutant levels. Overall, our research provides increased understanding on the physical, chemical, and biological controls of salmon contaminant biotransport in the Great Lakes region. This research will help inform management decisions in this region with respect to legacy pollution, dam removal, stream connectivity, fish stocking, and non-native species in stream ecosystems

Simulation of Ground-Truth Validation Data Via Physically- and Statistically-Based Warps

Abstract. The problem of scarcity of ground-truth expert delineations of medi-cal image data is a serious one that impedes the training and validation of medi-cal image analysis techniques. We develop an algorithm for the automatic generation of large databases of annotated images from a single reference data-set. We provide a web-based interface through which the users can upload a reference data set (an image and its corresponding segmentation and landmark points), provide custom setting of parameters, and, following server-side com-putations, generate and download an arbitrary number of novel ground-truth data, including segmentations, displacement vector fields, intensity non-uniformity maps, and point correspondences. To produce realistic simulated data, we use variational (statistically-based) and vibrational (physically-based) spatial deformations, nonlinear radiometric warps mimicking imaging non-homogeneity, and additive random noise with different underlying distributions. We outline the algorithmic details, present sample results, and provide the web address to readers for immediate evaluation and usage

Joint Attention and Brain Functional Connectivity in Infants and Toddlers

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development