Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth.

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multimodal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared with term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.

Notes on fiber length measurements: A case study in the underbelly of open source neuroscience.

Being on the bleeding edge of research requires the use of new and regularly updated software. The result is the occasional and inevitable occurrence of bugs. In the following work we present a case study where a feature request introduced a bug in a neuroimaging software package, which had consequences for the quality of results in a published article. We discuss the process of diagnosis, rectification and analysis replication.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

The Graded Change in Connectivity across the Ventromedial Prefrontal Cortex Reveals Distinct Subregions.

The functional heterogeneity of the ventromedial prefrontal cortex (vmPFC) suggests it may include distinct functional subregions. To date these have not been well elucidated. Regions with differentiable connectivity (and as a result likely dissociable functions) may be identified using emergent data-driven approaches. However, prior parcellations of the vmPFC have only considered hard splits between distinct regions, although both hard and graded connectivity changes may exist. Here we determine the full pattern of change in structural and functional connectivity across the vmPFC for the first time and extract core distinct regions. Both structural and functional connectivity varied along a dorsomedial to ventrolateral axis from relatively dorsal medial wall regions to relatively lateral basal orbitofrontal cortex. The pattern of connectivity shifted from default mode network to sensorimotor and multimodal semantic connections. This finding extends the classical distinction between primate medial and orbital regions by demonstrating a similar gradient in humans for the first time. Additionally, core distinct regions in the medial wall and orbitofrontal cortex were identified that may show greater correspondence to functional differences than prior hard parcellations. The possible functional roles of the orbitofrontal cortex and medial wall are discussed.

A tutorial and tool for exploring feature similarity gradients with MRI data.

There has been an increasing interest in examining organisational principles of the cerebral cortex (and subcortical regions) using different MRI features such as structural or functional connectivity. Despite the widespread interest, introductory tutorials on the underlying technique targeted for the novice neuroimager are sparse in the literature. Articles that investigate various "neural gradients" (for example based on region studied "cortical gradients," "cerebellar gradients," "hippocampal gradients" etc … or feature of interest "functional gradients," "cytoarchitectural gradients," "myeloarchitectural gradients" etc …) have increased in popularity. Thus, we believe that it is opportune to discuss what is generally meant by "gradient analysis". We introduce basics concepts in graph theory, such as graphs themselves, the degree matrix, and the adjacency matrix. We discuss how one can think about gradients of feature similarity (the similarity between timeseries in fMRI, or streamline in tractography) using graph theory and we extend this to explore such gradients across the whole MRI scale; from the voxel level to the whole brain level. We proceed to introduce a measure for quantifying the level of similarity in regions of interest. We propose the term "the Vogt-Bailey index" for such quantification to pay homage to our history as a brain mapping community. We run through the techniques on sample datasets including a brain MRI as an example of the application of the techniques on real data and we provide several appendices that expand upon details. To maximise intuition, the appendices contain a didactic example describing how one could use these techniques to solve a particularly pernicious problem that one may encounter at a wedding. Accompanying the article is a tool, available in both MATLAB and Python, that enables readers to perform the analysis described in this article on their own data. We refer readers to the graphical abstract as an overview of the analysis pipeline presented in this work.

Fiber length profiling: A novel approach to structural brain organization.

There has been a recent increased interest in the structural connectivity of the cortex. However, an important feature of connectivity remains relatively unexplored; tract length. In this article, we develop an approach to characterize fiber length distributions across the human cerebral cortex. We used data from 76 participants of the Adult WU-Minn Human Connectome Project using probabilistic tractography. We found that connections of different lengths are not evenly distributed across the cortex. They form patterns where certain areas have a high density of fibers of a specific length while other areas have very low density. To assess the relevance of these new maps in relation to established characteristics, we compared them to structural indices such as cortical myelin content and cortical thickness. Additionally, we assessed their relation to resting state network organization. We noted that areas with very short fibers have relatively more myelin and lower cortical thickness while the pattern is inverted for longer fibers. Furthermore, the cortical fiber length distributions produce specific correlation patterns with functional resting state networks. Specifically, we find evidence that as resting state networks increase in complexity, their length profiles change. The functionally more complex networks correlate with maps of varying lengths while primary networks have more restricted correlations. We posit that these maps are a novel way of differentiating between 'local modules' that have restricted connections to 'neighboring' areas and 'functional integrators' that have more far reaching connectivity.

An emergent functional parcellation of the temporal cortex.

The temporal lobe has been associated with various cognitive functions which include memory, auditory cognition and semantics. However, at a higher level of conceptualisation, all of the functions associated with the temporal lobe can be considered as lying along one major axis; from modality-specific to modality-general processing. This paper used a spectral reordering technique on resting-state and task-based functional data to extract the major organisational axis of the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations were performed on resting-state scans from 71 participants and active semantic task scans from 23 participants acquired using dual echo gradient echo planar imaging in order to preserve signal in inferior temporal cortex. The resulting organisational axis was consistent (over dataset and hemisphere) and progressed from superior temporal gyrus and posterior inferior temporal cortex to ventrolateral anterior temporal cortex. A hard parcellation separated a posterior (superior temporal and posterior fusiform and inferior temporal gyri) and an anterior cluster (ventrolateral anterior temporal lobe). The functional connectivity of the hard clusters supported the hypothesis that the connectivity gradient separated modality-specific and modality-general regions. This hypothesis was then directly tested by performing a VOI analysis upon an independent semantic task-based data set including auditory and visually presented stimuli. This confirmed that the ventrolateral anterior aspects of the temporal lobe are associated with modality-general processes whilst posterior and superior aspects are specific to certain modalities, with the posterior inferior subregions involved in visual processes and superior regions involved in audition.

A graded tractographic parcellation of the temporal lobe.

The temporal lobe has been implicated in multiple cognitive domains through lesion studies as well as cognitive neuroimaging research. There has been a recent increased interest in the structural and connective architecture that underlies these functions. However there has not yet been a comprehensive exploration of the patterns of connectivity that appear across the temporal lobe. This article uses a data driven, spectral reordering approach in order to understand the general axes of structural connectivity within the temporal lobe. Two important findings emerge from the study. Firstly, the temporal lobe's overarching patterns of connectivity are organised along two key structural axes: medial to lateral and anteroventral to posterodorsal, mirroring findings in the functional literature. Secondly, the connective organisation of the temporal lobe is graded and transitional; this is reminiscent of the original work of 19th Century neuroanatomists, who posited the existence of some regions which transitioned between one another in a graded fashion. While regions with unique connectivity exist, the boundaries between these are not always sharp. Instead there are zones of graded connectivity reflecting the influence and overlap of shared connectivity.

Local gradient analysis of human brain function using the Vogt-Bailey Index.

In this work, we take a closer look at the Vogt-Bailey (VB) index, proposed in Bajada et al. (NeuroImage 221:117140, 2020) as a tool for studying local functional homogeneity in the human cortex. We interpret the VB index in terms of the minimum ratio cut, a scaled cut-set weight that indicates whether a network can easily be disconnected into two parts having a comparable number of nodes. In our case, the nodes of the network consist of a brain vertex/voxel and its neighbours, and a given edge is weighted according to the affinity of the nodes it connects (as reflected by the modified Pearson correlation between their fMRI time series). Consequently, the minimum ratio cut quantifies the degree of small-scale similarity in brain activity: the greater the similarity, the 'heavier' the edges and the more difficult it is to disconnect the network, hence the higher the value of the minimum ratio cut. We compare the performance of the VB index with that of the Regional Homogeneity (ReHo) algorithm, commonly used to assess whether voxels in close proximity have synchronised fMRI signals, and find that the VB index is uniquely placed to detect sharp changes in the (local) functional organization of the human cortex.

Geometric effects of volume-to-surface mapping of fMRI data.

In this work, we identify a problem with the process of volume-to-surface mapping of functional Magnetic Resonance Imaging (fMRI) data that emerges in local connectivity analysis. We show that neighborhood correlations on the surface of the brain vary spatially with the gyral structure, even when the underlying volumetric data are uncorrelated noise. This could potentially have impacted studies focusing upon local neighborhood connectivity. We explore the effects of this anomaly across varying data resolutions and surface mesh densities, and propose several measures to mitigate these unwanted effects.

Occipital Intralobar fasciculi: a description, through tractography, of three forgotten tracts.

Diffusion MRI paired with tractography has facilitated a non-invasive exploration of many association, projection, and commissural fiber tracts. However, there is still a scarcity of research studies related to intralobar association fibers. The Dejerines' (two of the most notable neurologists of 19th century France) gave an in-depth description of the intralobar fibers of the occipital lobe. Unfortunately, their exquisite work has since been sparsely cited in the modern literature. This work gives a modern description of many of the occipital intralobar lobe fibers described by the Dejerines. We perform a virtual dissection and reconstruct the tracts using diffusion MRI tractography. The dissection is guided by the Dejerines' treatise, Anatomie des Centres Nerveux. As an accompaniment to this article, we provided a French-to-English translation of the treatise portion concerning five intra-occipital tracts, namely: the stratum calcarinum, the stratum proprium cunei, the vertical occipital fasciculus of Wernicke, the transverse fasciculus of the cuneus and the transverse fasciculus of the lingual lobule of Vialet. It was possible to reconstruct all but one of these tracts. For completeness, the recently described sledge runner fasciculus, although not one of the Dejerines' tracts, was identified and successfully reconstructed.

A structural connectivity convergence zone in the ventral and anterior temporal lobes: Data-driven evidence from structural imaging.

The hub-and-spoke model of semantic cognition seeks to reconcile embodied views of a fully distributed semantic network with patient evidence, primarily from semantic dementia, who demonstrate modality-independent conceptual deficits associated with atrophy centred on the ventrolateral anterior temporal lobe. The proponents of this model have recently suggested that the temporal cortex is a graded representational space where concepts become less linked to a specific modality as they are processed farther away from primary and secondary sensory cortices and towards the ventral anterior temporal lobe. To explore whether there is evidence that the connectivity patterns of the temporal lobe converge in its ventral anterior end the current study uses three dimensional Laplacian eigenmapping, a technique that allows visualisation of similarity in a low dimensional space. In this space similarity is encoded in terms of distances between data points. We found that the ventral and anterior temporal lobe is in a unique position of being at the centre of mass of the data points within the connective similarity space. This can be interpreted as the area where the connectivity profiles of all other temporal cortex voxels converge. This study is the first to explicitly investigate the pattern of connectivity and thus provides the missing link in the evidence that the ventral anterior temporal lobe can be considered a multi-modal graded hub.

The tract terminations in the temporal lobe: Their location and associated functions.

Temporal lobe networks are associated with multiple cognitive domains. Despite an upsurge of interest in connectional neuroanatomy, the terminations of the main fibre tracts in the human brain are yet to be mapped. This information is essential given that neurological, neuroanatomical and computational accounts expect neural functions to be strongly shaped by the pattern of white-matter connections. This paper uses a probabilistic tractography approach to identify the main cortical areas that contribute to the major temporal lobe tracts. In order to associate the tract terminations to known functional domains of the temporal lobe, eight automated meta-analyses were performed using the Neurosynth database. Overlaps between the functional regions highlighted by the meta-analyses and the termination maps were identified in order to investigate the functional importance of the tracts of the temporal lobe. The termination maps are made available in the Supplementary Materials of this article for use by researchers in the field.

Transport for language south of the Sylvian fissure: The routes and history of the main tracts and stations in the ventral language network.

It is now ten years since a 'ventral language pathway' was demonstrated in vivo in the human brain. In the intervening decade, this result has been replicated and expanded to include multiple possible pathways and functions. Despite this considerable level of research interest, age-old debates regarding the origin, course, termination and, indeed, the very existence of the tracts identified still remain. The current review examines four major tracts associated with the ventral 'semantic' language network, with the aim of elucidating and clarifying their structural and functional roles. Historical and modern conceptualisations of the tracts' neuroanatomical origins and terminations will be discussed, and key discrepancies and debates examined. It is argued that much of the controversy regarding the language pathways has resulted from inconsistencies in terminology, and the lack of a white matter 'lingua franca'.