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.

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.

The variation of function across the human insula mirrors its patterns of structural connectivity: evidence from in vivo probabilistic tractography.

The human insula is a functionally complex yet poorly understood region of the cortex, implicated in a wide range of cognitive, motor, emotion and somatosensory activity. To elucidate the functional role of the insula, the current study used in vivo probabilistic tractography to map the structural connectivity of seven anatomically-defined insular subregions. The connectivity patterns identified reveal two complementary insular networks connected via a dual route architecture, and provide key insights about the neural basis of the numerous functions ascribed to this area. Specifically, anterior-most insular regions were associated with a ventrally-based network involving orbital/inferior frontal and anterior/polar temporal regions, forming part of a key emotional salience and cognitive control network associated with the implementation of goal-directed behavior. The posterior and dorsal-middle insular regions were associated with a network focused on posterior and (to a lesser extent) anterior temporal regions via both dorsal and ventral pathways. This is consistent with the involvement of the insula in sound-to-speech transformations, with an implicated role in the temporal resolution, sequencing, and feedback processes crucial for auditory and motor processing, and the monitoring and adjustment of expressive performance.

Exploring distinct default mode and semantic networks using a systematic ICA approach.

Resting-state networks (RSNs; groups of regions consistently co-activated without an explicit task) are hugely influential in modern brain research. Despite this popularity, the link between specific RSNs and their functions remains elusive, limiting the impact on cognitive neuroscience (where the goal is to link cognition to neural systems). Here we present a series of logical steps to formally test the relationship between a coherent RSN with a cognitive domain. This approach is applied to a challenging and significant test-case; extracting a recently-proposed semantic RSN, determining its relation with a well-known RSN, the default mode network (DMN), and assessing their roles in semantic cognition. Results showed the DMN and semantic network are two distinct coherent RSNs. Assessing the cognitive signature of these spatiotemporally coherent networks directly (and therefore accounting for overlapping networks) showed involvement of the proposed semantic network, but not the DMN, in task-based semantic cognition. Following the steps presented here, researchers could formally test specific hypotheses regarding the function of RSNs, including other possible functions of the DMN.

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 structural connectivity of higher order association cortices reflects human functional brain networks.

Human higher cognition arises from the main tertiary association cortices including the frontal, temporal and parietal lobes. Many studies have suggested that cortical functions must be shaped or emerge from the pattern of underlying physical (white matter) connectivity. Despite the importance of this hypothesis, there has not been a large-scale analysis of the white-matter connectivity within and between these associative cortices. Thus, we explored the pattern of intra- and inter-lobe white matter connectivity between multiple areas defined in each lobe. We defined 43 regions of interest on the lateral associative cortex cytoarchitectonically (6 regions of interest - ROIs in the frontal lobe and 17 ROIs in the parietal lobe) and anatomically (20 ROIs in the temporal lobe) on individuals' native space. The results demonstrated that intra-region connectivity for all 3 lobes was dense and graded generally. In contrary, the inter-lobe connectivity was relatively discrete and regionally specific such that only small sub-regions exhibited long-range connections to another lobe. The long-range connectivity was mediated by 6 major associative white matter tracts, consistent with the notion that these higher cognitive functions arises from brain-wide distributed connectivity. Using graph-theory network analysis we revealed five physically-connected sub-networks, which correspond directly to five known functional networks. This study provides strong and direct evidence that core functional brain networks mirror the brain's structural connectivity.

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'.

Interaction between dorsal and ventral processing streams: where, when and how?

The execution of complex visual, auditory, and linguistic behaviors requires a dynamic interplay between spatial ('where/how') and non-spatial ('what') information processed along the dorsal and ventral processing streams. However, while it is acknowledged that there must be some degree of interaction between the two processing networks, how they interact, both anatomically and functionally, is a question which remains little explored. The current review examines the anatomical, temporal, and behavioral evidence regarding three potential models of dual stream interaction: (1) computations along the two pathways proceed independently and in parallel, reintegrating within shared target brain regions; (2) processing along the separate pathways is modulated by the existence of recurrent feedback loops; and (3) information is transferred directly between the two pathways at multiple stages and locations along their trajectories.

Using in vivo probabilistic tractography to reveal two segregated dorsal 'language-cognitive' pathways in the human brain.

Primate studies have recently identified the dorsal stream as constituting multiple dissociable pathways associated with a range of specialized cognitive functions. To elucidate the nature and number of dorsal pathways in the human brain, the current study utilized in vivo probabilistic tractography to map the structural connectivity associated with subdivisions of the left supramarginal gyrus (SMG). The left SMG is a prominent region within the dorsal stream, which has recently been parcellated into five structurally-distinct regions which possess a dorsal-ventral (and rostral-caudal) organisation, postulated to reflect areas of functional specialisation. The connectivity patterns reveal a dissociation of the arcuate fasciculus into at least two segregated pathways connecting frontal-parietal-temporal regions. Specifically, the connectivity of the inferior SMG, implicated as an acoustic-motor speech interface, is carried by an inner/ventro-dorsal arc of fibres, whilst the pathways of the posterior superior SMG, implicated in object use and cognitive control, forms a parallel outer/dorso-dorsal crescent.

Connectivity-based structural and functional parcellation of the human cortex using diffusion imaging and tractography.

The parcellation of the cortex via its anatomical properties has been an important research endeavor for over a century. To date, however, a universally accepted parcellation scheme for the human brain still remains elusive. In the current review, we explore the use of in vivo diffusion imaging and white matter tractography as a non-invasive method for the structural and functional parcellation of the human cerebral cortex, discussing the strengths and limitations of the current approaches. Cortical parcellation via white matter connectivity is based on the premise that, as connectional anatomy determines functional organization, it should be possible to segregate functionally-distinct cortical regions by identifying similarities and differences in connectivity profiles. Recent studies have provided initial evidence in support of the efficacy of this connectional parcellation methodology. Such investigations have identified distinct cortical subregions which correlate strongly with functional regions identified via fMRI and meta-analyses. Furthermore, a strong parallel between the cortical regions defined via tractographic and more traditional cytoarchitectonic parcellation methods has been observed. However, the degree of correspondence and relative functional importance of cytoarchitectonic- versus connectivity-derived parcellations still remains unclear. Diffusion tractography remains one of the only methods capable of visualizing the structural networks of the brain in vivo. As such, it is of vital importance to continue to improve the accuracy of the methodology and to extend its potential applications in the study of cognition in neurological health and disease.

Neuroanatomical correlates of oral reading in acute left hemispheric stroke.

Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional imaging can identify cortical regions engaged in the process under examination, it cannot identify those brain regions essential for the task. The current study aimed to identify those neuroanatomical regions critical for successful oral reading by examining the relationship between word and nonword oral reading deficits and areas of tissue dysfunction in acute stroke. We evaluated 91 patients with left hemisphere ischemic stroke with a test of oral word and nonword reading, and magnetic resonance diffusion-weighted and perfusion-weighted imaging, within 24-48h of stroke onset. A voxel-wise statistical map showed that impairments in word and nonword reading were associated with a distributed network of brain regions, including the inferior and middle frontal gyri, the middle temporal gyrus, the supramarginal and angular gyri, and the middle occipital gyrus. In addition, lesions associated with word deficits were found to be distributed more frontally, while nonword deficits were associated with lesions distributed more posteriorly.

Patterns of reading performance in acute stroke: A descriptive analysis.

UNLABELLED: One of the main sources of information regarding the underlying processes involved in both normal and impaired reading has been the study of reading deficits that occur as a result of brain damage. However, patterns of reading deficits found acutely after brain injury have been little explored. The observed patterns of performance in chronic stroke patients might reflect reorganization of the cognitive processes underlying reading or development of compensatory strategies that are not normally used to read. METHOD: 112 acute left hemisphere stroke patients were administered a task of oral reading of words and pseudowords within 1-2 days of hospital admission; performance was examined for error rate and type, and compared to that on tasks involving visual lexical decision, visual/auditory comprehension, and naming. RESULTS: Several distinct patterns of performance were identified. Although similarities were found between the patterns of reading performance observed acutely and the classical acquired dyslexias generally identified more chronically, some notable differences were observed. Of interest was the finding that no patient produced any pure semantic errors in reading, despite finding such errors in comprehension and naming.