Topographic Connectivity Research Articles

Topographical Information-Based High-Order Functional Connectivity and Its Application in Abnormality Detection forMild Cognitive Impairment.

Temporal synchronization-based functional connectivity (FC) has long been used by the neuroscience community. However, topographical FC information may provide additional information to characterize the advanced relationship between two brain regions. Accordingly, we proposed a novel method, namely high-order functional connectivity (HOFC), to capture this second-level relationship using inter-regional resemblance of the FC topographical profiles. Specifically, HOFC first calculates an FC profile for each brain region, notably between the given brain region and other brain regions. Based on these FC profiles, a second layer of correlations is computed between all pairs of brain regions (i.e., correlation's correlation). On this basis, we generated an HOFC network, where "high-order" network properties were computed. We found that HOFC was discordant with the traditional FC in several links, indicating additional information being revealed by the new metrics. We applied HOFC to identify biomarkers for early detection of Alzheimer's disease by comparing 77 mild cognitive impairment patients with 89 healthy individuals (control group). Sensitivity in detection of group difference was consistently improved by ∼25% using HOFC compared to using FC. An HOFC network analysis also provided complementary information to an FC network analysis. For example, HOFC between olfactory and orbitofrontal cortices was found significantly reduced in patients, besides extensive alterations in HOFC network properties. In conclusion, our results showed promise in using HOFC to comprehensively map the human brain connectome.

Defining thalamic nuclei and topographic connectivity gradients in vivo

The thalamus consists of multiple nuclei that have been previously defined by their chemoarchitectual and cytoarchitectual properties ex vivo. These form discrete, functionally specialized, territories with topographically arranged graduated patterns of connectivity. However, previous in vivo thalamic parcellation with MRI has been hindered by substantial inter-individual variability or discrepancies between MRI derived segmentations and histological sections.Here, we use the Euclidean distance to characterize probabilistic tractography distributions derived from diffusion MRI. We generate 12 feature maps by performing voxel-wise parameterization of the distance histograms (6 feature maps) and the distribution of three-dimensional distance transition gradients generated by applying a Sobel kernel to the distance metrics. We use these 12 feature maps to delineate individual thalamic nuclei, then extract the tractography profiles for each and calculate the voxel-wise tractography gradients. Within each thalamic nucleus, the tractography gradients were topographically arranged as distinct non-overlapping cortical networks with transitory overlapping mid-zones.This work significantly advances quantitative segmentation of the thalamus in vivo using 3T MRI. At an individual subject level, the thalamic segmentations consistently achieve a close relationship with a priori histological atlas information, and resolve in vivo topographic gradients within each thalamic nucleus for the first time. Additionally, these techniques allow individual thalamic nuclei to be closely aligned across large populations and generate measures of inter-individual variability that can be used to study both basic function and pathological processes in vivo.

Impact of topography on groundwater salinization due to ocean surge inundation

AbstractSea‐level rise and increases in the frequency and intensity of ocean surges caused by climate change are likely to exacerbate adverse effects on low‐lying coastal areas. The landward flow of water during ocean surges introduces salt to surficial coastal aquifers and threatens groundwater resources. Coastal topographic features (e.g., ponds, dunes, barrier islands, and channels) likely have a strong impact on overwash and salinization processes, but are generally highly simplified in modeling studies. To understand topographic impacts on groundwater salinization, we modeled a theoretical overwash event and variable‐density groundwater flow and salt transport in 3‐D using the fully coupled surface and subsurface numerical simulator, HydroGeoSphere. The model simulates the coastal aquifer as an integrated system considering overland flow, coupled surface and subsurface exchange, variably saturated flow, and variable‐density groundwater flow. To represent various coastal landscape types, we simulated both synthetic fields and real‐world coastal topography from Delaware, USA. The groundwater salinization assessment suggested that the topographic connectivity promoting overland flow controls the volume of aquifer that is salinized. In contrast, the amount of water that can be stored in surface depressions determines the amount of seawater that infiltrates the subsurface and the time for seawater to flush from the aquifer. Our study suggests that topography has a significant impact on groundwater salinization due to ocean surge overwash, with important implications for coastal land management and groundwater vulnerability assessment.

Topographical functional connectivity patterns exist in the congenitally, prelingually deaf.

Congenital deafness causes large changes in the auditory cortex structure and function, such that without early childhood cochlear-implant, profoundly deaf children do not develop intact, high-level, auditory functions. But how is auditory cortex organization affected by congenital, prelingual, and long standing deafness? Does the large-scale topographical organization of the auditory cortex develop in people deaf from birth? And is it retained despite cross-modal plasticity? We identified, using fMRI, topographic tonotopy-based functional connectivity (FC) structure in humans in the core auditory cortex, its extending tonotopic gradients in the belt and even beyond that. These regions show similar FC structure in the congenitally deaf throughout the auditory cortex, including in the language areas. The topographic FC pattern can be identified reliably in the vast majority of the deaf, at the single subject level, despite the absence of hearing-aid use and poor oral language skills. These findings suggest that large-scale tonotopic-based FC does not require sensory experience to develop, and is retained despite life-long auditory deprivation and cross-modal plasticity. Furthermore, as the topographic FC is retained to varying degrees among the deaf subjects, it may serve to predict the potential for auditory rehabilitation using cochlear implants in individual subjects.

Neuroanatomy: The added value of the Klingler method

Undergraduate neuroanatomy students are usually not able to achieve a clear comprehension of the spatial relationships existing between the white matter fiber tracts in spite of numerous neuroanatomy textbooks, atlases and multimedia tools.The objective of this paper is to show the educational value of the application of the Klingler fiber dissection technique and the use of these dissections in the understanding of the three-dimensional intrinsic anatomy of the brain white matter for medical students.Four formalin-fixed brains were dissected using the Klingler methodology in order to reveal the inner anatomical organization of the brain white matter. The most important fiber systems were dissected and their relationships to the cerebral and cerebellar gray matter structures visualized. These dissections were used as a learning tool in teaching the brain white matter structural and topographical connectivity. The white matter fiber systems were presented to undergraduate medical students during a neuroanatomy course. They observed and manipulated the dissected specimens leading to a thorough understanding of the configuration and location of the white matter fiber tracts, and their relationships to the ventricular system and gray matter structures. Subsequently, students were asked to answer a survey concerning the importance of the utilization of this material in their understanding of the three-dimensional intrinsic anatomy of the brain white matter. The knowledge acquired with this technique, complemented by conventional formalin-fixed sections may improve the neuroanatomical knowledge and future retention of medical students.

A potential role for overland dispersal in shaping aquatic invertebrate communities in arid regions

Summary Traditionally, dispersal of aquatic invertebrates has been thought to be very closely associated with river network structure, despite many species being capable of active or passive dispersal across the terrestrial matrix. However, recent studies of both population genetics and community structure from dryland regions indicate that aquatic species commonly disperse across catchments, implying that movement away from streams is more common than originally thought. This study investigated how aquatic invertebrate metacommunity structure in central Australia is influenced by interactions between species’ dispersal traits, dispersal routes and local environmental conditions. We sampled community composition in 16 perennial and long‐term inundated freshwater habitats in central Australia. Aquatic invertebrate taxa were allocated to one of four dispersal trait groups: obligate aquatic, passive aerial, weak flying and strong flying. We then used Mantel tests to examine correlations between trait group community dissimilarities, and four isolation models representing (i) local environmental conditions, (ii) geographical distances, (iii) landscape resistances restricted to river networks and (iv) landscape resistances incorporating overland dispersal ‘conduits’. We found that the community composition of aquatic invertebrates in three of four dispersal trait groups, and all traits combined, was influenced primarily by topographic connectivity via overland dispersal conduits. Our results suggest that rainfall events and their effect on the landscape as a whole, rather than river flow during these events, shape aquatic invertebrate metacommunity structure in central Australia. This study provides further support for the importance of overland dispersal conduits to aquatic invertebrates, particularly in arid environments with irregular rainfall.

Topographical Information-Based High-Order Functional Connectivity and Its Application in Abnormality Detection for Mild Cognitive Impairment

Topographical Information-Based High-Order Functional Connectivity and Its Application in Abnormality Detection for Mild Cognitive Impairment

The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map.

The mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the development of the olfactory sensory map are beginning to be elucidated. Little is known about mechanisms by which sensory stimuli shape the organization of the map after birth. We show that a stimulus-dependent gradient of a retinoic acid-inactivating enzyme Cyp26B1 modifies the composition, localization, and axonal projections of olfactory sensory neuron classes. The mechanism is novel and suggests the interesting possibility that local vitamin A metabolism could also be a mediator of stimulus-dependent modifications of precise spatial connectivity in other parts of the nervous system.

Hoxa2 Selects Barrelette Neuron Identity and Connectivity in the Mouse Somatosensory Brainstem.

Mouse whiskers are somatotopically mapped in brainstem trigeminal nuclei as neuronal modules known as barrelettes. Whisker-related afferents form barrelettes in ventral principal sensory (vPrV) nucleus, whereas mandibular input targets dorsal PrV (dPrV). How barrelette neuron identity and circuitry is established is poorly understood. We found that ectopic Hoxa2 expression in dPrV neurons is sufficient to attract whisker-related afferents, induce asymmetrical dendrite arbors, and allow ectopic barrelette map formation. Moreover, the thalamic area forming whisker-related barreloids is prenatally targeted by both vPrV and dPrV axons followed by perinatal large-scale pruning of dPrV axons and refinement of vPrV barrelette input. Ectopic Hoxa2 expression allows topographically directed targeting and refinement of dPrV axons with vPrV axons into a single whisker-related barreloid map. Thus, a single HOX transcription factor is sufficient to switch dPrV into a vPrV barrelette neuron program and coordinate input-output topographic connectivity of a dermatome-specific circuit module.

Biophysical Mind Units and Leibniz’s Law in Practice

Objectives: Externally absorbed/translated or internally retrieved from memory storage mobile biophysical mind units [bmu], stimulate immobile inseparable topographical neuronal webs connectivity, to intimately attach to ions to travel them via their channels media, to be measured based on Leibniz's law from fMRI, PET and EEG presentations. Background: Brain-Mind dilemma is replaced with the inseparable immobile neuronal web wiring matter media through which mobile bmu matter have been processed. Method: An Internet search for articles displaying measured data obtained from fMRI, PET and EEG pertaining to mind processes via topographical brain was performed. I paraphrased Lebni'z formulae for bmu = a3 × wf/bf/t, in which 1 bmu is the product of (a³) 1 mm³ volume of operable basic logic circuits presets with bmu measured from fMRI, PET and EEG multiplied by cfn (coefficient frequency number) obtained from working frequency (wf: bf=cn) to basal frequency (bf) of EEG at awake onset (8/8=1ncf) and divided by 1 second, tested from the left frontal lobe at full rest. Results: Must include: a) identical random sample inclusion, b) Identical fMRI+EEG, PET+EEG types of measurements, c) identical mental tasks, d) identical basal data that support life sustenance manipulating mental activation regions. I found no two similar methods out of articles meeting a, b, c, and d criteria. Conclusion: In practical terms my model may promote a) detection and measurement of specialized webs connectivity or neuronal basic logic circuit presets processing bmu, b) simulation of Artificial Intelligence (AI) and c) creation of a humanoid robot technology based on emulating human biophysical mind qualities.

Reproducibility of Functional Connectivity and Graph Measures Based on the Phase Lag Index (PLI) and Weighted Phase Lag Index (wPLI) Derived from High Resolution EEG

Functional connectivity (FC) and graph measures provide powerful means to analyze complex networks. The current study determines the inter-subject-variability using the coefficient of variation (CoV) and long-term test-retest-reliability (TRT) using the intra-class correlation coefficient (ICC) in 44 healthy subjects with 35 having a follow-up at years 1 and 2. FC was estimated from 256-channel-EEG by the phase-lag-index (PLI) and weighted PLI (wPLI) during an eyes-closed resting state condition. PLI quantifies the asymmetry of the distribution of instantaneous phase differences of two time-series and signifies, whether a consistent non-zero phase lag exists. WPLI extends the PLI by additionally accounting for the magnitude of the phase difference. Signal-space global and regional PLI/wPLI and weighted first-order graph measures, i.e. normalized clustering coefficient (gamma), normalized average path length (lambda), and the small-world-index (SWI) were calculated for theta-, alpha1-, alpha2- and beta-frequency bands. Inter-subject variability of global PLI was low to moderate over frequency bands (0.12<CoV<0.28), higher for wPLI (0.25<CoV<0.55) and very low for gamma, lambda and SWI (CoV<0.048). TRT was good to excellent for global PLI/wPLI (0.68<ICC<0.80), regional PLI/wPLI (0.58<ICC<0.77), and fair to good for graph measures (0.32<ICC<0.73) except wPLI-based lambda in alpha1 (ICC = 0.12). Inter-electrode distance correlated very weakly with inter-electrode PLI (−0.06<rho<0) and weakly with inter-electrode wPLI (−0.22<rho<−0.18). Global PLI/wPLI and topographic connectivity patterns differed between frequency bands, and all individual networks showed a small-world-configuration. PLI/wPLI based network characterization derived from high-resolution EEG has apparently good reliability, which is one important requirement for longitudinal studies exploring the effects of chronic brain diseases over several years.

Activity-dependent and graded BACE1 expression in the olfactory epithelium is mediated by the retinoic acid metabolizing enzyme CYP26B1.

It is well established that environmental influences play a key role in sculpting neuronal connectivity in the brain. One example is the olfactory sensory map of topographic axonal connectivity. While intrinsic odorant receptor signaling in olfactory sensory neurons (OSN) determines anterior-posterior counter gradients of the axonal guidance receptors Neuropilin-1 and Plexin-A1, little is known about stimulus-dependent gradients of protein expression, which correlates with the functional organization of the olfactory sensory map along its dorsomedial (DM)-ventrolateral (VL) axis. Deficiency of the Alzheimer's β-secretase BACE1, which is expressed in a DM(low)-VL(high) gradient, results in OSN axon targeting errors in a DM>VL and gene dose-dependent manner. We show that expression of BACE1 and the all-trans retinoic acid (RA)-degrading enzyme Cyp26B1 form DM-VL counter gradients in the olfactory epithelium. Analyses of mRNA and protein levels in OSNs after naris occlusion, in mice deficient in the olfactory cyclic nucleotide-gated channel and in relation to onset of respiration, show that BACE1 and Cyp26B1 expression in OSNs inversely depend on neuronal activity. Overexpression of a Cyp26B1 or presence of a dominant negative RA receptor transgene selectively in OSNs, inhibit BACE1 expression while leaving the DM(low)-VL(high) gradient of the axonal guidance protein Neuropilin-2 intact. We conclude that stimulus-dependent neuronal activity can control the expression of the RA catabolic enzyme Cyp26B1 and downstream genes such as BACE1. This result is pertinent to an understanding of the mechanisms by which a topographic pattern of connectivity is achieved and modified as a consequence of graded gene expression and sensory experience.

Hox genes and region‐specific sensorimotor circuit formation in the hindbrain and spinal cord

Homeobox (Hox) genes were originally discovered in the fruit fly Drosophila, where they function through a conserved homeodomain as transcriptional regulators to control embryonic morphogenesis. In vertebrates, 39 Hox genes have been identified and like their Drosophila counterparts they are organized within chromosomal clusters. Hox genes interact with various cofactors, such as the TALE homeodomain proteins, in recognition of consensus sequences within regulatory elements of their target genes. In vertebrates, Hox genes display spatially restricted patterns of expression within the developing hindbrain and spinal cord, and are considered crucial determinants of segmental identity and cell specification along the anterioposterior and dorsoventral axes of the embryo. Here, we review their later roles in the assembly of neuronal circuitry, in stereotypic neuronal migration, axon pathfinding, and topographic connectivity. Importantly, we will put some emphasis on how their early-segmented expression patterns can influence the formation of complex vital hindbrain and spinal cord circuitries.

Involvement of EphB1 Receptors Signalling in Models of Inflammatory and Neuropathic Pain

EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy. In sensory systems, they play a role in both the onset of inflammatory and neuropathic pain, and in the establishment of central sensitisation, an NMDA-mediated form of synaptic plasticity thought to underlie most forms of chronic pain. We studied wild type and EphB1 knockout mice in a range of inflammatory and neuropathic pain models to determine 1), whether EphB1 expression is necessary for the onset and/or maintenance of persistent pain, regardless of origin; 2), whether in these models cellular and molecular changes, e.g. phosphorylation of the NR2B subunit of the NMDA receptor, increased c-fos expression or microglial activation, associated with the onset of pain, are affected by the lack of functional EphB1 receptors. Differences in phenotype were examined behaviourally, anatomically, biochemically and electrophysiologically. Our results establish firstly, that functional EphB1 receptors are not essential for the development of normal nociception, thermal or mechanical sensitivity. Secondly, they demonstrate a widespread involvement of EphB1 receptors in chronic pain. NR2B phosphorylation, c-fos expression and microglial activation are all reduced in EphB1 knockout mice. This last finding is intriguing, since microglial activation is supposedly triggered directly by primary afferents, therefore it was not expected to be affected. Interestingly, in some models of long-term pain (days), mechanical and thermal hyperalgesia develop both in wild type and EphB1 knockout mice, but recovery is faster in the latter, indicating that in particular models these receptors are required for the maintenance, rather than the onset of, thermal and mechanical hypersensitivity. This potentially makes them an attractive target for analgesic strategies.

EphA Signaling Impacts Development of Topographic Connectivity in Auditory Corticofugal Systems

Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of EphA receptor signaling in the development of corticothalamic (CT) and corticocollicular connections. Early in postnatal development, CT axons were restricted to a deep dorsal zone (DDZ) within the MGB that expressed low levels of the ephrin-A ligand. By hearing onset, CT axons had innervated surrounding regions of MGB in control-electroporated mice but remained fixed within the DDZ in mice overexpressing EphA7. In vivo neurophysiological recordings demonstrated a corresponding reduction in spontaneous firing rate, but no changes in sound-evoked responsiveness within MGB regions deprived of CT innervation. Structural and functional CT disruption occurred without gross alterations in thalamocortical connectivity. These data demonstrate a potential role for EphA/ephrin-A signaling in the initial guidance of corticofugal axons and suggest that "genetic rewiring" may represent a useful functional tool to alter cortical feedback without silencing Actx.

Topographically specific functional connectivity between visual field maps in the human brain

Neural activity in mammalian brains exhibits large spontaneous fluctuations whose structure reveals the intrinsic functional connectivity of the brain on many spatial and temporal scales. Between remote brain regions, spontaneous activity is organized into large-scale functional networks. To date, it has remained unclear whether the intrinsic functional connectivity between brain regions scales down to the fine detail of anatomical connections, for example the fine-grained topographic connectivity structure in visual cortex. Here, we show that fMRI signal fluctuations reveal a detailed retinotopically organized functional connectivity structure between the visual field maps of remote areas of the human visual cortex. The structured coherent fluctuations were even preserved in complete darkness when all visual input was removed. While the topographic connectivity structure was clearly visible in within hemisphere connections, the between hemisphere connectivity structure differs for representations along the vertical and horizontal meridian respectively. These results suggest a tight link between spontaneous neural activity and the fine-grained topographic connectivity pattern of the human brain. Thus, intrinsic functional connectivity reflects the detailed connectivity structure of the cortex at a fine spatial scale. It might thus be a valuable tool to complement anatomical studies of the human connectome, which is one of the keys to understand the functioning of the human brain.

Sperry versus Hebb: Topographic mapping in Isl2/EphA3 mutant mice

BackgroundIn wild-type mice, axons of retinal ganglion cells establish topographically precise projection to the superior colliculus of the midbrain. This means that axons of neighboring retinal ganglion cells project to the proximal locations in the target. The precision of topographic projection is a result of combined effects of molecular labels, such as Eph receptors and ephrins, and correlated neural activity. In the Isl2/EphA3 mutant mice the expression levels of molecular labels are changed. As a result the topographic projection is rewired so that the neighborhood relationships between retinal cell axons are disrupted.ResultsHere we study the computational model for retinocollicular connectivity formation that combines the effects of molecular labels and correlated neural activity. We argue that the effects of correlated activity presenting themselves in the form of Hebbian learning rules can facilitate the restoration of the topographic connectivity even when the molecular labels carry conflicting instructions. This occurs because the correlations in electric activity carry information about retinal cells' origin that is independent on molecular labels. We argue therefore that partial restoration of the topographic property of the retinocollicular projection observed in Isl2/EphA3 heterozygous knockin mice may be explained by the effects of correlated neural activity. We address the maps observed in Isl2/EphA3 knockin/EphA4 knockout mice in which the levels of retinal labels are uniformly reduced. These maps can be explained by either the saturation of EphA receptor mapping leading to the relative signaling model or by the reverse signaling conveyed by ephrin-As expressed by retinal axons.ConclusionAccording to our model, experiments in Isl2/EphA3 knock-in mice test the interactions between effects of molecular labels and correlated activity during the development of neural connectivity. Correlated activity can partially restore topographic order even when molecular labels carry conflicting information.

Mapping the face in the somatosensory brainstem

The facial somatosensory map in the cortex is derived from facial representations that are first established at the brainstem level and then serially 'copied' at each stage of the somatosensory pathway. Recent studies have provided insights into the molecular mechanisms involved in the development of somatotopic maps of the face and whiskers in the trigeminal nuclei of the mouse brainstem. This work has revealed that early molecular regionalization and positional patterning of trigeminal ganglion and brainstem target neurons are established by homeodomain transcription factors, the expression of which is induced and maintained by signals from the brain and face. Such position-dependent information is fundamental in transforming the early spatial layout of sensory receptors into a topographic connectivity map that is conferred to higher brain levels.

Abnormal strategies during visual discrimination reversal learning in ephrin-A2−/− mice

Eph receptors and ephrins are involved in establishing topographic connectivity in primary sensory brain regions, but also in higher order structures including the cortex and hippocampus. Ephrin-A2 −/− mice have abnormal topography in the primary visual system but have normal visual and learning performance on a simple visual discrimination task. Here we use signal detection theory to analyse learning behaviour of these mice. Wild-type (WT) and ephrin-A2 −/− (KO) mice performed equally well in a two-stimulus visual discrimination task, with similar learning rates and response latencies. However, during reversal learning, when the rewarded stimulus was switched, the two genotypes exhibited differences in response strategies: while WTs favoured a win-stay strategy, KOs remained relatively neutral. KOs also exhibited a stronger lateralization bias in the initial stages of learning, choosing the same arm of the maze with high probability. In addition, use of a Bayesian “optimal observer” revealed that compared to WT, KO mice adapted their decisions less rapidly to a change in stimulus-reward relationship. We suggest that the misexpression of ephrin-A2 may lead to abnormal connectivity in regions known for their involvement in reversal learning and perseverative behaviours, including thalamic–prefrontal cortical–striatal circuitry and particularly orbitofrontal cortex. The implication is that topographic organisation of higher order brain regions may play an important role in learning and decision making.

An open Google Earth for neuroinformatics: The Whole Brain Catalog

An open Google Earth for neuroinformatics: The Whole Brain Catalog