Intact Bilateral Resting-State Networks in the Absence of the Corpus Callosum

Temporal correlations between different brain regions in the resting-state BOLD signal are thought to reflect intrinsic functional brain connectivity (Biswal et al., 1995; Greicius et al., 2003; Fox et al., 2007). The functional networks identified are typically bilaterally distributed across the cerebral hemispheres, show similarity to known white matter connections (Greicius et al., 2009), and are seen even in anesthetized monkeys (Vincent et al., 2007). Yet it remains unclear how they arise. Here we tested two distinct possibilities: (1) functional networks arise largely from structural connectivity constraints, and generally require direct interactions between functionally coupled regions mediated by white-matter tracts; and (2) functional networks emerge flexibly with the development of normal cognition and behavior and can be realized in multiple structural architectures. We conducted resting-state fMRI in eight adult humans with complete agenesis of the corpus callosum (AgCC) and normal intelligence, and compared their data to those from eight healthy matched controls. We performed three main analyses: anatomical region-of-interest-based correlations to test homotopic functional connectivity, independent component analysis (ICA) to reveal functional networks with a data-driven approach, and ICA-based interhemispheric correlation analysis. Both groups showed equivalently strong homotopic BOLD correlation. Surprisingly, almost all of the group-level independent components identified in controls were observed in AgCC and were predominantly bilaterally symmetric. The results argue that a normal complement of resting-state networks and intact functional coupling between the hemispheres can emerge in the absence of the corpus callosum, favoring the second over the first possibility listed above

Regional requirements for Dishevelled signaling during Xenopus gastrulation: separable effects on blastopore closure, mesendoderm internalization and archenteron formation

During amphibian gastrulation, the embryo is transformed by the combined actions of several different tissues. Paradoxically, many of these morphogenetic processes can occur autonomously in tissue explants, yet the tissues in intact embryos must interact and be coordinated with one another in order to accomplish the major goals of gastrulation: closure of the blastopore to bring the endoderm and mesoderm fully inside the ectoderm, and generation of the archenteron. Here, we present high-resolution 3D digital datasets of frog gastrulae, and morphometrics that allow simultaneous assessment of the progress of convergent extension, blastopore closure and archenteron formation in a single embryo. To examine how the diverse morphogenetic engines work together to accomplish gastrulation, we combined these tools with time-lapse analysis of gastrulation, and examined both wild-type embryos and embryos in which gastrulation was disrupted by the manipulation of Dishevelled (Xdsh) signaling. Remarkably, although inhibition of Xdsh signaling disrupted both convergent extension and blastopore closure, mesendoderm internalization proceeded very effectively in these embryos. In addition, much of archenteron elongation was found to be independent of Xdsh signaling, especially during the second half of gastrulation. Finally, even in normal embryos, we found a surprising degree of dissociability between the various morphogenetic processes that occur during gastrulation. Together, these data highlight the central role of PCP signaling in governing distinct events of Xenopus gastrulation, and suggest that the loose relationship between morphogenetic processes may have facilitated the evolution of the wide variety of gastrulation mechanisms seen in different amphibian species

The Claustrum and Insula in Microcebus murinus: A High Resolution Diffusion Imaging Study

The claustrum and the insula are closely juxtaposed in the brain of the prosimian primate, the gray mouse lemur (Microcebus murinus). Whether the claustrum has closer affinities with the cortex or the striatum has been debated for many decades. Our observation of histological sections from primate brains and genomic data in the mouse suggest former. Given this, the present study compares the connections of the two structures in Microcebus using high angular resolution diffusion imaging (HARDI, with 72 directions), with a very small voxel size (90 micra), and probabilistic fiber tractography. High angular and spatial resolution diffusion imaging is non-destructive, requires no surgical interventions, and the connection of each and every voxel can be mapped, whereas in conventional tract tracer studies only a few specific injection sites can be assayed. Our data indicate that despite the high genetic and spatial affinities between the two structures, their connectivity patterns are very different. The claustrum connects with many cortical areas and the olfactory bulb; its strongest probabilistic connections are with the entorhinal cortex, suggesting that the claustrum may have a role in spatial memory and navigation. By contrast, the insula connects with many subcortical areas, including the brainstem and thalamic structures involved in taste and visceral feelings. Overall, the connections of the Microcebus claustrum and insula are similar to those of the rodents, cat, macaque, and human, validating our results. The insula in the Microcebus connects with the dorsolateral frontal cortex in contrast to the mouse insula, which has stronger connections with the ventromedial frontal lobe, yet this is consistent with the dorsolateral expansion of the frontal cortex in primates. In addition to revealing the connectivity patterns of the Microcebus brain, our study demonstrates that HARDI, at high resolutions, can be a valuable tool for mapping fiber pathways for multiple sites in fixed brains in rare and difficult-to-obtain species

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to controls. Design: A cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and nine amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age. Results: CAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions. Conclusions: This study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are particularly affected within the medial temporal lobes in CAH youth

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T_1- and T_2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivoprobabilistic anatomical atlas of the human brain

Effect of Inversion Recovery Fat Suppression on Hepatic R2* Quantitation in Transfusional Siderosis

OBJECTIVE. The purpose of this study is to evaluate whether the application of spectral pre-saturation inversion recovery (SPIR) fat suppression in standard multiecho gradient-echo sequences has a significant effect on hepatic R2* quantitation in patients with iron overload syndromes. MATERIALS AND METHODS. Eighty patients were scanned with a multiecho gradient-echo sequence without and with the application of SPIR. Six different postprocessing approaches were used to extract R2* values for maximum generality. RESULTS. SPIR fat suppression lowered R2* values by 3.9–7.0% (p < 0.0001 in all pairwise comparisons), independently of the postprocessing algorithm. Coefficients of variation for R2* ranged from 4.5% to 10.0%. Regardless of the size of the ROI (area of homogeneous tissue or entire liver profile in the slice), pixelwise approaches combined with an exponential-plus-constant fitting model yielded the lowest coefficients of variation (4.5% and 5.1%), whereas truncated exponential fits of the averaged signals produced the highest coefficients of variation (7.8% and 10%). For R2* values exceeding 200 Hz, a Bland-Altman analysis showed a bias that grew linearly for all postprocessing methods. CONCLUSION. SPIR fat suppression resulted in systematically lower hepatic R2* estimates. Because calibration curves were derived using images without fat suppression, these biases should be corrected when reporting liver iron concentrations estimated from fat-suppressed multiecho T2*-weighted images

Personal space regulation by the human amygdala

The amygdala plays key roles in emotion and social cognition, but how this translates to face-to-face interactions involving real people remains unknown. We found that an individual with complete amygdala lesions lacked any sense of personal space. Furthermore, healthy individuals showed amygdala activation upon close personal proximity. The amygdala may be required to trigger the strong emotional reactions normally following personal space violations, thus regulating interpersonal distance in humans

High-field diffusion MR histology: Image-based correction of eddy-current ghosts in diffusion-weighted rapid acquisition with relaxation enhancement (DW-RARE)

High-resolution, diffusion-weighted (DW) MR microscopy is gaining increasing acceptance as a nondestructive histological tool for the study of fixed tissue samples. Spin-echo sequences are popular for high-field diffusion imaging due to their high tolerance to B_0 field inhomogeneities. Volumetric DW rapid acquisition with relaxation enhancement (DW-RARE) currently offers the best tradeoff between imaging efficiency and image quality, but is relatively sensitive to residual eddy-current effects on the echo train phase, resulting in encoding direction-dependent ghosting in the DW images. We introduce two efficient, image-based phase corrections for ghost artifact reduction in DW-RARE of fixed tissue samples, neither of which require navigator echo acquisition. Both methods rely on the phase difference in k-space between the unweighted reference image and a given DW image and assume a constant, per-echo phase error arising from residual eddy-current effects in the absence of sample motion. Significant qualitative and quantitative ghost artifact reductions are demonstrated for individual DW and calculated diffusion tensor images

Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism

Autism spectrum disorder (ASD) features profound social deficits but neuroimaging studies have failed to find any consistent neural signature. Here we connect these two facts by showing that idiosyncratic patterns of brain activation are associated with social comprehension deficits. Human participants with ASD (N = 17) and controls (N = 20) freely watched a television situation comedy (sitcom) depicting seminaturalistic social interactions (“The Office”, NBC Universal) in the scanner. Intersubject correlations in the pattern of evoked brain activation were reduced in the ASD group—but this effect was driven entirely by five ASD subjects whose idiosyncratic responses were also internally unreliable. The idiosyncrasy of these five ASD subjects was not explained by detailed neuropsychological profile, eye movements, or data quality; however, they were specifically impaired in understanding the social motivations of characters in the sitcom. Brain activation patterns in the remaining ASD subjects were indistinguishable from those of control subjects using multiple multivariate approaches. Our findings link neurofunctional abnormalities evoked by seminaturalistic stimuli with a specific impairment in social comprehension, and highlight the need to conceive of ASD as a heterogeneous classification

High efficiency, low distortion 3D diffusion tensor imaging with variable density spiral fast spin echoes (3D DW VDS RARE)

We present an acquisition and reconstruction method designed to acquire high resolution 3D fast spin echo diffusion tensor images while mitigating the major sources of artifacts in DTI-field distortions, eddy currents and motion. The resulting images, being 3D, are of high SNR, and being fast spin echoes, exhibit greatly reduced field distortions. This sequence utilizes variable density spiral acquisition gradients, which allow for the implementation of a self-navigation scheme by which both eddy current and motion artifacts are removed. The result is that high resolution 3D DTI images are produced without the need for eddy current compensating gradients or B_0 field correction. In addition, a novel method for fast and accurate reconstruction of the non-Cartesian data is employed. Results are demonstrated in the brains of normal human volunteers