Anterior-posterior Gradient Research Articles

Dissociable functional responses along the posterior-anterior gradient of the frontal and parietal cortices revealed by parametric working memory and training.

While the storage capacity is limited, accumulating studies have indicated that working memory (WM) can be improved by cognitive training. However, understanding how exactly the brain copes with limited WM capacity and how cognitive training optimizes the brain remains inconclusive. Given the hierarchical functional organization of WM, we hypothesized that the activation profiles along the posterior-anterior gradient of the frontal and parietal cortices characterize WM load and training effects. To test this hypothesis, we recruited 51 healthy volunteers and adopted a parametric WM paradigm and training method. In contrast to exclusively strengthening the activation of posterior areas, a broader range of activation concurrently occurred in the anterior areas to cope with increased memory load for all subjects at baseline. Moreover, there was an imbalance in the responses of the posterior and anterior areas to the same increment of 1 item at different load levels. Although a general decrease in activation after adaptive training, the changes in the posterior and anterior areas were distinct at different memory loads. Particularly, we found that the activation gradient between the posterior and anterior areas was significantly increased at load 4-back after adaptive training, and the changes were correlated with improvement in WM performance. Together, our results demonstrate a shift in the predominant role of posterior and anterior areas in the frontal and parietal cortices when approaching WM capacity limits. Additionally, the training-induced performance improvement likely benefits from the elevated neural efficiency reflected in the increased activation gradient between the posterior and anterior areas.

Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification.

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas1,2. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation5,6,7,8. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization6,10. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Functional organization of the human corpus callosum unveiled with BOLD-fMRI gradients

Abstract Gradients capture the underlying functional organization of the brain. Cortical gradients have been well characterized, however very little is known about the underlying gradient of the white matter. Here, we proposed a functionally gradient mapping of the corpus callosum by using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI), which for the first time uncovered three distinct but stable spatial axes: posterior-anterior, dorsal-ventral, and left-right. The three spatial patterns were replicated in another independent cohort and robust across scanning conditions. We further associated the three gradient maps with brain anatomy, connectome, and task-related brain functions, by using structural magnetic resonance imaging, both resting-state and task fMRI, and diffusion tensor imaging data. The posterior-anterior gradient distribution of the corpus callosum showed a similar pattern with the cerebral cortex, gradually extending from the primary cortex to the transmodal cortex. The dorsal-ventral gradient distribution revealed an N-shaped pattern from the primary cortex to the higher-order cognitive cortex. The posterior-anterior and dorsal-ventral gradient maps were also associated with white-matter microstructures, such as fractional anisotropy and myelin water fraction. The left-right gradient showed an inverted V-shaped pattern, which delineated the inter-hemisphere separation. These findings provide fundamental insight into the functional organization of the human corpus callosum, unveiling potential patterns of functional interaction with the cerebral cortex and their associations with cognitive behaviors.

Sensitivity of Phonation Onset Pressure to Vocal Fold Stiffness Distribution.

Phonation onset is characterized by the unstable growth of vocal fold (VF) vibrations that ultimately results in self-sustained oscillation and the production of modal voice. Motivated by histological studies, much research has focused on the role of the layered structure of the vocal folds in influencing phonation onset, wherein the outer "cover" layer is relatively soft and the inner "body" layer is relatively stiff. Recent research, however, suggests that the body-cover (BC) structure over-simplifies actual stiffness distributions by neglecting important spatial variations, such as inferior-superior (IS) and anterior-posterior gradients and smooth transitions in stiffness from one histological layer to another. Herein, we explore sensitivity of phonation onset to stiffness gradients and smoothness. By assuming no a priori stiffness distribution and considering a second-order Taylor series sensitivity analysis of phonation onset pressure with respect to stiffness, we find two general smooth stiffness distributions most strongly influence onset pressure: a smooth stiffness containing aspects of BC differences and IS gradients in the cover, which plays a role in minimizing onset pressure, and uniform increases in stiffness, which raise onset pressure and frequency. While the smooth stiffness change contains aspects qualitatively similar to layered BC distributions used in computational studies, smooth transitions in stiffness result in higher sensitivity of onset pressure than discrete layering. These two general stiffness distributions also provide a simple, low-dimensional, interpretation of how complex variations in VF stiffness affect onset pressure, enabling refined exploration of the effects of stiffness distributions on phonation onset.

Population-wide cerebellar growth models of children and adolescents

In the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using a total of 7240 neuroimaging scans from 4862 individuals, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence (age range: 6–17 years), an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.

Three-dimensional histology reveals dissociable human hippocampal long-axis gradients of Alzheimer's pathology.

Three-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without a magnetic resonance imaging (MRI) reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimer's disease. Blockface photographs of brain hemisphere slices are used for 3D reconstruction, from which an MRI-like image is generated using machine learning. Histology sections are aligned to the reconstructed hemisphere and subsequently to an atlas in standard space. Path2MR successfully registered histological sections to their anatomic position along the hippocampal longitudinal axis. Combined with histopathology quantification, we found an expected peak of tau pathology at the anterior end of the hippocampus, whereas amyloid-beta (Aβ) displayed a quadratic anterior-posterior distribution. Path2MR, which enables 3D histology using any brain bank data set, revealed significant differences along the hippocampus between tau and Aβ. Path2MR enables three-dimensional (3D) brain reconstruction from blockface dissection photographs. This pipeline does not require dense specimen sampling or a subject-specific magnetic resonance (MR) image. Anatomically consistent mapping of hippocampal sections was obtained with Path2MR. Our analyses revealed an anterior-posterior gradient of hippocampal tau pathology. In contrast, the peak of amyloid-beta (Aβ) deposition was closer to the hippocampal body.

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns

BackgroundThis study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns.MethodsWe recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures.ResultsTwo distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons.ConclusionsThe findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.

Graded functional organization in the left inferior frontal gyrus: evidence from task-free and task-based functional connectivity.

The left inferior frontal gyrus has been ascribed key roles in numerous cognitive domains, such as language and executive function. However, its functional organization is unclear. Possibilities include a singular domain-general function, or multiple functions that can be mapped onto distinct subregions. Furthermore, spatial transition in function may be either abrupt or graded. The present study explored the topographical organization of the left inferior frontal gyrus using a bimodal data-driven approach. We extracted functional connectivity gradients from (i) resting-state fMRI time-series and (ii) coactivation patterns derived meta-analytically from heterogenous sets of task data. We then sought to characterize the functional connectivity differences underpinning these gradients with seed-based resting-state functional connectivity, meta-analytic coactivation modeling and functional decoding analyses. Both analytic approaches converged on graded functional connectivity changes along 2 main organizational axes. An anterior-posterior gradient shifted from being preferentially associated with high-level control networks (anterior functional connectivity) to being more tightly coupled with perceptually driven networks (posterior). A second dorsal-ventral axis was characterized by higher connectivity with domain-general control networks on one hand (dorsal functional connectivity), and with the semantic network, on the other (ventral). These results provide novel insights into an overarching graded functional organization of the functional connectivity that explains its role in multiple cognitive domains.

Distinct Lateral Prefrontal Regions Are Organized in an Anterior-Posterior Functional Gradient.

The dorsolateral prefrontal cortex (dlPFC) is composed of multiple anatomically defined regions involved in higher-order cognitive processes, including working memory and selective attention. It is organized in an anterior-posterior global gradient where posterior regions track changes in the environment, whereas anterior regions support abstract neural representations. However, it remains unknown if such a global gradient results from a smooth gradient that spans regions or an emergent property arising from functionally distinct regions, that is, an areal gradient. Here, we recorded single neurons in the dlPFC of nonhuman primates trained to perform a memory-guided saccade task with an interfering distractor and analyzed their physiological properties along the anterior-posterior axis. We found that these physiological properties were best described by an areal gradient. Further, population analyses revealed that there is a distributed representation of spatial information across the dlPFC. Our results validate the functional boundaries between anatomically defined dlPFC regions and highlight the distributed nature of computations underlying working memory across the dlPFC.SIGNIFICANCE STATEMENT Activity of frontal lobe regions is known to possess an anterior-posterior functional gradient. However, it is not known whether this gradient is the result of individual brain regions organized in a gradient (like a staircase), or a smooth gradient that spans regions (like a slide). Analysis of physiological properties of individual neurons in the primate frontal regions suggest that individual regions are organized as a gradient, rather than a smooth gradient. At the population level, working memory was more prominent in posterior regions, although it was also present in anterior regions. This is consistent with the functional segregation of brain regions that is also observed in other systems (i.e., the visual system).

Quantitative and Qualitative Representation of Introductory and Advanced EEG Concepts: An Exploration of Different EEG Setups.

Electroencephalograms (EEGs) are the gold standard test used in the medical field to diagnose epilepsy and aid in the diagnosis of many other neurological and mental disorders. Growing in popularity in terms of nonmedical applications, the EEG is also used in research, neurofeedback, and brain-computer interface, making it increasingly relevant to student learning. Recent innovations have made EEG setups more accessible and affordable, thus allowing their integration into neuroscience educational settings. Introducing students to EEGs, however, can be daunting due to intricate setup protocols, individual variation, and potentially expensive equipment. This paper aims to provide guidance for introducing students and educators to fundamental beginning and advanced level EEG concepts. Specifically, this paper tested the potential of three different setups, with varying channel number and wired or wireless connectivity, for introducing students to qualitative and quantitative exploration of alpha enhancement when eyes are closed, and observation of the alpha/beta anterior to posterior gradient. The setups were compared to determine their relative advantages and their robustness in detecting these well-established parameters. The basic 1- or 2-channel setups are sufficient for observing alpha and beta waves, while more advanced systems containing 8 or 16 channels are required for consistent observation of an anterior-posterior gradient. In terms of localization, the 16-channel setup, in principle, was more adept. The 8-channel setup, however, was more effective than the 16-channel setup with regards to displaying the anterior to posterior gradient. Thus, an 8-channel setup is sufficient in an education setting to display these known trends. Modification of the 16-channel setup may provide a better observation of the anterior to posterior gradient.

A novel histological staging of hippocampal sclerosis that is evident in gray matter loss in vivo.

Hippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology. We studied 159 brain donations from the multimodal Vallecas Alzheimer's Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and magnetic resonance imaging (MRI) data. Our HS staging system displayed a significant correlation with disease duration, cognitive performance, and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anterior-posterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal gray matter density as a function of HS staging. The association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS. The definition of hippocampal sclerosis of aging (HS) is currently limited to an end-stage pathological fingerprint. We characterize early HS histological features to define a complete staging system. The proposed staging displays a parallel but not identical progression to limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE). The proposed staging also reflects the expected demographic and cognitive differences associated with HS. In vivo magnetic resonance imaging (MRI) showed focal hippocampal gray matter loss as a function of HS staging.

Conserved structures of neural activity in sensorimotor cortex of freely moving rats allow cross-subject decoding

Our knowledge about neuronal activity in the sensorimotor cortex relies primarily on stereotyped movements that are strictly controlled in experimental settings. It remains unclear how results can be carried over to less constrained behavior like that of freely moving subjects. Toward this goal, we developed a self-paced behavioral paradigm that encouraged rats to engage in different movement types. We employed bilateral electrophysiological recordings across the entire sensorimotor cortex and simultaneous paw tracking. These techniques revealed behavioral coupling of neurons with lateralization and an anterior–posterior gradient from the premotor to the primary sensory cortex. The structure of population activity patterns was conserved across animals despite the severe under-sampling of the total number of neurons and variations in electrode positions across individuals. We demonstrated cross-subject and cross-session generalization in a decoding task through alignments of low-dimensional neural manifolds, providing evidence of a conserved neuronal code.

Anterior-posterior gradient in the integrated processing of forelimb movement direction and distance in macaque parietal cortex.

A major issue in modern neuroscience is to understand how cell populations present multiple spatial and motor features during goal-directed movements. The direction and distance (depth) of arm movements often appear to be controlled independently during behavior, but it is unknown whether they share neural resources or not. Using information theory, singular value decomposition, and dimensionality reduction methods, we compare direction and depth effects and their convergence across three parietal areas during an arm movement task. All methods show a stronger direction effect during early movement preparation, whereas depth signals prevail during movement execution. Going from anterior to posterior sectors, we report an increased number of cells processing both signals and stronger depth effects. These findings suggest a serial direction and depth processing consistent with behavioral evidence and reveal a gradient of joint versus independent control of these features in parietal cortex that supports its role in sensorimotor transformations.

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation.

Progesterone treatment is commonly employed to promote and support pregnancy. While maternal tissues are the main progesterone targets in humans and mice, its receptor (PGR) is expressed in the murine embryo, questioning its function during embryonic development. Progesterone has been previously associated with murine blastocyst development. Whether it contributes to lineage specification is largely unknown. Gastrulation initiates lineage specification and generation of the progenitors contributing to all organs. Cells passing through the primitive streak (PS) will give rise to the mesoderm and endoderm. Cells emerging posteriorly will form the extraembryonic mesodermal tissues supporting embryonic growth. Cells arising anteriorly will contribute to the embryonic heart in two sets of distinct progenitors, first (FHF) and second heart field (SHF). We found that PGR is expressed in a posterior–anterior gradient in the PS of gastrulating embryos. We established in vitro differentiation systems inducing posterior (extraembryonic) and anterior (cardiac) mesoderm to unravel PGR function. We discovered that PGR specifically modulates extraembryonic and cardiac mesoderm. Overexpression experiments revealed that PGR safeguards cardiac differentiation, blocking premature SHF progenitor specification and sustaining the FHF progenitor pool. This role of PGR in heart development indicates that progesterone administration should be closely monitored in potential early-pregnancy patients undergoing infertility treatment.

Developmental pattern of association fibers and their interaction with associated cortical microstructures in 0–5-month-old infants

Association fibers connect the cortical regions and experience rapid development involving myelination and axonal growth during infancy. Yet, the spatiotemporal patterns of microstructural changes along these tracts, as well as the developmental interaction between the white matter (WM) tracts and the cortical gray matter (cGM) connected to them, are mostly unknown during infancy. In this study, we performed a diffusion MRI-based tractography and microstructure study in a cohort of 89 healthy preterm-born infants with gestational age at birth between 28.1∼36.4 weeks and postmenstrual age at scan between 39.9∼59.9 weeks. Results revealed that several C-shaped fibers, such as the arcuate fasciculus, cingulum, and uncinate fasciculus, demonstrated symmetrical along-tract profiles; and the horizontally oriented running fibers, including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus, demonstrated an anterior-posterior developmental gradient. This study characterized the along-tract profiles using fixel-based analysis and revealed that the fiber cross-section (FC) of all five association fibers demonstrated a fluctuating increase with age, while the fiber density (FD) monotonically increase with age. NODDI was utilized to analyze the microstructural development of cGM and indicated cGM connected to the anterior end of the association fibers developed faster than that of the posterior end during 0–5 months. Notably, a mediation analysis was used to explore the relation between the development of WM and associated cGM, and demonstrated a partial mediation effect of FD in WM on the development of intracellular volume (ICV) in cGM and a full mediation effect of ICV on the growth of FD in most fibers, suggesting a predominant mediation of cGM on the WM development. Furthermore, for assessing whether those results were biased by prematurity, we compared preterm- and term-born neonates with matched scan age, gender, and multiple births from the developing human connectome project (dHCP) dataset to assess the effect of preterm-birth, and the results indicated a similar developmental pattern of the association fibers and their attached cGM. These findings presented a comprehensive picture of the major association fibers during early infancy and deciphered the developmental interaction between WM and cGM in this period.

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

The prevailing network perspective of Parkinson’s disease (PD) emerges not least from the ascending neuropathology traceable in histological studies. However, whether longitudinal in vivo correlates of network degeneration in PD can be observed remains unresolved. Here, we applied a trimodal imaging protocol combining 18F-fluorodeoxyglucose (FDG)- and 18F-fluoro-L-Dopa- (FDOPA)-PET with resting-state functional MRI to assess longitudinal changes in midbrain metabolism, striatal dopamine depletion and striatocortical dysconnectivity in 17 well-characterized PD patients. Whole-brain (un)paired-t-tests with focus on midbrain or striatum were performed between visits and in relation to 14 healthy controls (HC) in PET modalities. Resulting clusters of FDOPA-PET comparisons provided volumes for seed-based functional connectivity (FC) analyses between visits and in relation to HC. FDG metabolism in the left midbrain decreased compared to baseline along with caudatal FDOPA-uptake. This caudate cluster exhibited a longitudinal FC decrease to sensorimotor and frontal areas. Compared to healthy subjects, dopamine-depleted putamina indicated stronger decline in striatocortical FC at follow-up with respect to baseline. Increasing nigrostriatal deficits and striatocortical decoupling were associated with deterioration in motor scores between visits in repeated-measures correlations. In summary, our results demonstrate the feasibility of in-vivo tracking of progressive network degeneration using a multimodal imaging approach. Specifically, our data suggest advancing striatal and widespread striatocortical dysfunction via an anterior-posterior gradient originating from a hypometabolic midbrain cluster within a well-characterized and only mild to moderately affected PD cohort during a relatively short period.

Bias field correction in hyperpolarized 129 Xe ventilation MRI using templates derived by RF-depolarization mapping.

To correct for RF inhomogeneity for in vivo 129 Xe ventilation MRI using flip-angle mapping enabled by randomized 3D radial acquisitions. To extend this RF-depolarization mapping approach to create a flip-angle map template applicable to arbitrary acquisition strategies, and to compare these approaches to conventional bias field correction. RF-depolarization mapping was evaluated first in digital simulations and then in 51 subjects who had undergone radial 129 Xe ventilation MRI in the supine position at 3T (views=3600; samples/view=128; TR/TE=4.5/0.45 ms; flip angle=1.5; FOV=40 cm). The images were corrected using newly developed RF-depolarization and templated-based methods and the resulting quantitative ventilation metrics (mean, coefficient of variation, and gradient) were compared to those resulting from N4ITK correction. RF-depolarization and template-based mapping methods yielded a pattern of RF-inhomogeneity consistent with the expected variation based on coil architecture. The resulting corrected images were visually similar, but meaningfully distinct from those generated using standard N4ITK correction. The N4ITK algorithm eliminated the physiologically expected anterior-posterior gradient (-0.04 ± 1.56%/cm, P < 0.001). These 2 newly introduced methods of RF-depolarization and template correction retained the physiologically expected anterior-posterior ventilation gradient in healthy subjects (2.77 ± 2.09%/cm and 2.01 ± 2.73%/cm, respectively). Randomized 3D 129 Xe MRI ventilation acquisitions can inherently be corrected for bias field, and this technique can be extended to create flip angle templates capable of correcting images from a given coil regardless of acquisition strategy. These methods may be more favorable than the de facto standard N4ITK because they can remove undesirable heterogeneity caused by RF effects while retaining results from known physiology.

Rectified random cell motility as a mechanism for embryo elongation.

The body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the tail bud. The tail bud is a source of highly motile cells that eventually constitute the presomitic mesoderm (PSM), a tissue that plays an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient that parallels a gradient associated with the degradation of a specific cellular signal (FGF) known to be implicated in cell motility. Here, we combine the electroporation of fluorescent reporters in the PSM with time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that a simple microscopic model for random cell motility induced by FGF activity along with geometric confinement leads to rectified tissue elongation consistent with our observations. A continuum analog of the microscopic model leads to a macroscopic mechano-chemical model for tissue extension that couples FGF activity-induced cell motility and tissue rheology, and is consistent with the experimentally observed speed and extent of elongation. Together, our experimental observations and theoretical models explain how the continuous addition of cells at the tail bud combined with lateral confinement can be converted into oriented movement and drive body elongation.

Functional parcellation of the hippocampus based on its layer-specific connectivity with default mode and dorsal attention networks

Recent neuroimaging evidence suggests that there might be an anterior-posterior functional differentiation of the hippocampus along the long-axis. The HERNET (hippocampal encoding/retrieval and network) model proposed an encoding/retrieval dichotomy with the anterior hippocampus more connected to the dorsal attention network (DAN) during memory encoding, and the posterior portions more connected to the default mode network (DMN) during retrieval. Evidence both for and against the HERNET model has been reported. In this study, we test the validity of the HERNET model non-invasively in humans by computing functional connectivity (FC) in layer-specific cortico-hippocampal microcircuits. This was achieved by acquiring sub-millimeter functional magnetic resonance imaging (fMRI) data during encoding/retrieval tasks at 7T. Specifically, FC between infra-granular output layers of DAN with hippocampus during encoding and FC between supra-granular input layers of DMN with hippocampus during retrieval were computed to test the predictions of the HERNET model. Our results support some predictions of the HERNET model including anterior-posterior gradient along the long axis of the hippocampus. While preferential relationships between the entire hippocampus and DAN/DMN during encoding/retrieval, respectively, were observed as predicted, anterior-posterior specificity in these network relationships could not be confirmed. The strength and clarity of evidence for/against the HERNET model were superior with layer-specific data compared to conventional volume data.