Dorsal Fibers Research Articles

Lateralization of dorsal fiber tract targeting Broca’s area concurs with language skills during development

Language is bounded to the left hemisphere in the adult brain and the functional lateralization can already be observed early during development. Here we investigate whether this is paralleled by a lateralization of the white matter structural language network. We analyze the strength and microstructural properties of language-related fiber tracts connecting temporal and frontal cortices with a separation of two dorsal tracts, one targeting the posterior Broca’s area (BA44) and one targeting the precentral gyrus (BA6). In a large sample of young children (3–6 years), we demonstrate that, in contrast to the BA6-targeting tract, the microstructural asymmetry of the BA44-targeting fiber tract significantly correlates locally with different aspects of development. While the asymmetry in its anterior segment reflects age, the asymmetry in its posterior segment is associated with the children’s language skills. These findings demonstrate a fine-grained structure-to-function mapping in the lateralized network and go beyond our current view of language-related human brain maturation.

Statistical parametrization of cell cytoskeleton reveals lung cancer cytoskeletal phenotype with partial EMT signature

Epithelial–mesenchymal Transition (EMT) is a multi-step process that involves cytoskeletal rearrangement. Here, developing and using an image quantification tool, Statistical Parametrization of Cell Cytoskeleton (SPOCC), we have identified an intermediate EMT state with a specific cytoskeletal signature. We have been able to partition EMT into two steps: (1) initial formation of transverse arcs and dorsal stress fibers and (2) their subsequent conversion to ventral stress fibers with a concurrent alignment of fibers. Using the Orientational Order Parameter (OOP) as a figure of merit, we have been able to track EMT progression in live cells as well as characterize and quantify their cytoskeletal response to drugs. SPOCC has improved throughput and is non-destructive, making it a viable candidate for studying a broad range of biological processes. Further, owing to the increased stiffness (and by inference invasiveness) of the intermediate EMT phenotype compared to mesenchymal cells, our work can be instrumental in aiding the search for future treatment strategies that combat metastasis by specifically targeting the fiber alignment process.

DSCAM is differentially patterned along the optic axon pathway in the developing Xenopus visual system and guides axon termination at the target

BackgroundThe Xenopus retinotectal circuit is organized topographically, where the dorsal–ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the complement of molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards and innervate their target in the tectum, remains unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path and at their target.MethodsUsing a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, following to the optic nerve and chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We then assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum.ResultsHighest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Targeted downregulation of DSCAM expression on ventral RGCs affected the segregation of medial axon fibers from their dorsal counterparts within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization.ConclusionThese findings together with previous studies demonstrating cell-autonomous roles for DSCAM during the development of pre- and postsynaptic arbors in the Xenopus retinotectal circuit indicates that DSCAM exerts multiple roles in coordinating axon targeting and structural connectivity in the developing vertebrate visual system.

Diffusion MRI data, sulcal anatomy, and tractography for eight species from the Primate Brain Bank

Large-scale comparative neuroscience requires data from many species and, ideally, at multiple levels of description. Here, we contribute to this endeavor by presenting diffusion and structural MRI data from eight primate species that have not or rarely been described in the literature. The selected samples from the Primate Brain Bank cover a prosimian, New and Old World monkeys, and a great ape. We present preliminary labelling of the cortical sulci and tractography of the optic radiation, dorsal part of the cingulum bundle, and dorsal parietal–frontal and ventral temporal-frontal longitudinal white matter tracts. Both dorsal and ventral association fiber systems could be observed in all samples, with the dorsal tracts occupying much less relative volume in the prosimian than in other species. We discuss the results in the context of known primate specializations and present hypotheses for further research. All data and results presented here are available online as a resource for the scientific community.

Prediction of Stress Distribution Applied to the Triangular Fibrocartilage Complex: A Finite Element Analysis

PurposeThe triangular fibrocartilage complex (TFCC) is an important tissue stabilizer for the distal radioulnar joint, but stress distribution on the TFCC is not clear. The purpose of this study was to report the stress distribution of the TFCC using finite element analysis (FEA).MethodsPathological specimens of the wrist joint from an 80-year-old man were imported into a finite element analysis software package, and regions of interest including bone, soft tissue, and TFCC were extracted to create a 3-dimensional model. The material properties were obtained from previous research using cadaver specimens. To allow large deformations, we used hyperelastic elements to model the TFCC and soft tissue. Bone was defined as a uniform tissue that did not break. With the carpals and radius constrained, the rotation axis was set at the center of the ulnar head and a force was applied to move the ulnar head in pronation and supination. Under these boundary conditions, the behavior of the TFCC was extracted as a moving image. The average value of the maximum principal stress for each component of the TFCC was extracted and graphed.ResultsIn the supinated position, the maximum principal stress was found on the palmar side of the TFCC (eg, on the tension side). In pronation, the maximum principal stress was found on the dorsal side.ConclusionsThis study clearly showed the 3-dimensional structure of the TFCC and analyzed its stress distribution under load. In supination, mean values of the maximum principal stress were greater on the palmar fibers than the dorsal fibers. In pronation, mean maximum principal stress was greater on the dorsal fibers than the palmar fibers.Clinical relevanceKnowing the distribution of stresses in the TFCC is an important factor in developing treatment strategies for a pathologic TFCC.

Premotor dorsal white matter integrity for the prediction of upper limb motor impairment after stroke

Corticospinal tract integrity after stroke has been widely investigated through the evaluation of fibres descending from the primary motor cortex. However, about half of the corticospinal tract is composed by sub-pathways descending from premotor and parietal areas, to which damage may play a more specific role in motor impairment and recovery, particularly post-stroke. Therefore, the main aim of this study was to investigate lesion load within corticospinal tract sub-pathways as predictors of upper limb motor impairment after stroke. Motor impairment (Fugl-Meyer Upper Extremity score) was evaluated in 27 participants at one week and six months after stroke, together with other clinical and demographic data. Neuroimaging data were obtained within the first week after stroke. Univariate regression analysis indicated that among all neural correlates, lesion load within premotor fibres explained the most variance in motor impairment at six months (R2 = 0.44, p < 0.001). Multivariable regression analysis resulted in three independent, significant variables explaining motor impairment at six months; Fugl-Meyer Upper Extremity score at one week, premotor dorsal fibre lesion load at one week, and age below or above 70 years (total R2 = 0.81; p < 0.001). Early examination of premotor dorsal fibre integrity may be a promising biomarker of upper limb motor impairment after stroke.

Grayson Ligament: A Revised Description of its Anatomy and Function

Grayson ligament has been described as a common pathway for digital contracture in Dupuytren disease. Its anatomical descriptions in the literature are, however, inconsistent. We have performed a microsurgical dissection study in 20 fresh-frozen and thawed digits to revisit the anatomy of Grayson ligaments. We also performed dissections in Thiel-preserved hands to be able to study the changes in tension of the ligaments during flexion and extension of the finger. We found the ligaments originally described by Grayson to be the best developed part of a trabecular network of fibers, originating in continuity with the outer adventitial layer of the flexor tendon sheath and running toward their insertions into the skin in multiple planes, all volar to the neurovascular bundle. The most dorsal fibers, which cover the neurovascular bundles, form a chevron shape with its midline apex pointing distally in an extended finger. During flexion, the fibers become more transversely oriented. We found Grayson ligament comprises a trabecular network of fibers, instead of a ligament, with a dynamic fiber orientation on the volar side of the finger. The main function of this network of fibers seems to be the stabilization of the skin and fat pad in digit extension while the relaxation in flexion allows the skin and volar fat pad to adapt optimally to the form of the object that is held. The new insights in the anatomy of Grayson trabecular network of fibers may be of importance in the understanding of the pathological anatomy of Dupuytren disease.

Abnormal frontostriatal tracts in young male tobacco smokers

Dysfunctions in frontostriatal circuits have been associated with craving and cognitive control in smokers. However, the relevance of white matter (WM) diffusion properties of the ventral and dorsal frontostriatal tracts for behaviors associated with smoking remains relatively unknown, especially in young adulthood, a critical time period for the development and maintenance of addiction. Here, diffusion tensor imaging (DTI) and probabilistic tractography were used to investigate the WM tracts of the ventral and dorsal frontostriatal circuits in two independent studies (Study1: 36 male smokers (21.3 ± 1.3 years) vs. 35 male nonsmokers (21.2 ± 1.3 years); Study2: 29 male smokers (21.4 ± 1.1 years) vs. 25 male nonsmokers (21.0 ± 1.4 years)). Subjective craving was measured by the Questionnaire on Smoking Urges (QSU) and cognitive control ability was assessed with the Stroop task. In both studies, smokers committed more response errors than nonsmokers during the incongruent condition of the Stroop task. Relative to controls, smokers showed lower fractional anisotropy (FA) and higher radial diffusivity in left medial orbitofrontal cortex-to-nucleus accumbens fiber tracts (ventral frontostriatal path) and also lower FA in right dorsolateral prefrontal cortex-to-caudate fiber tracts (dorsal frontostriatal path). The FA values of the right dorsal fibers were negatively correlated with incongruent response Stroop errors in smokers, whereas the mean diffusivity values of the left ventral fibers were positively correlated with craving in smokers. Thus, WM diffusion properties of the dorsal and ventral frontostriatal tracts were associated with cognitive control and craving, respectively, in young male tobacco smokers. These data highlight the importance of studying WM in relation to neuropsychological changes underlying smoking.

White matter pathways for prosodic structure building: A case study

The relevance of left dorsal and ventral fiber pathways for syntactic and semantic comprehension is well established, while pathways for prosody are little explored. The present study examined linguistic prosodic structure building in a patient whose right arcuate/superior longitudinal fascicles and posterior corpus callosum were transiently compromised by a vasogenic peritumoral edema. Compared to ten matched healthy controls, the patient’s ability to detect irregular prosodic structure significantly improved between pre- and post-surgical assessment. This recovery was accompanied by an increase in average fractional anisotropy (FA) in right dorsal and posterior transcallosal fiber tracts. Neither general cognitive abilities nor (non-prosodic) syntactic comprehension nor FA in right ventral and left dorsal fiber tracts showed a similar pre-post increase. Together, these findings suggest a contribution of right dorsal and inter-hemispheric pathways to prosody perception, including the right-dorsal tracking and structuring of prosodic pitch contours that is transcallosally informed by concurrent syntactic information.

The assembly and function of perinuclear actin cap in migrating cells

Stress fibers are actin bundles encompassing actin filaments, actin-crosslinking, and actin-associated proteins that represent the major contractile system in the cell. Different types of stress fibers assemble in adherent cells, and they are central to diverse cellular processes including establishment of the cell shape, morphogenesis, cell polarization, and migration. Stress fibers display specific cellular organization and localization, with ventral fibers present at the basal side, and dorsal fibers and transverse actin arcs rising at the cell front from the ventral to the dorsal side and toward the nucleus. Perinuclear actin cap fibers are a specific subtype of stress fibers that rise from the leading edge above the nucleus and terminate at the cell rear forming a dome-like structure. Perinuclear actin cap fibers are fixed at three points: both ends are anchored in focal adhesions, while the central part is physically attached to the nucleus and nuclear lamina through the linker of nucleoskeleton and cytoskeleton (LINC) complex. Here, we discuss recent work that provides new insights into the mechanism of assembly and the function of these actin stress fibers that directly link extracellular matrix and focal adhesions with the nuclear envelope.

Evolution of the neural language network

The evolution of language correlates with distinct changes in the primate brain. The present article compares language-related brain regions and their white matter connectivity in the developing and mature human brain with the respective structures in the nonhuman primate brain. We will see that the functional specificity of the posterior portion of Broca’s area (Brodmann area [BA 44]) and its dorsal fiber connection to the temporal cortex, shown to support the processing of structural hierarchy in humans, makes a crucial neural difference between the species. This neural circuit may thus be fundamental for the human syntactic capacity as the core of language.

Subaxial cervical pedicle screw fixation through paraspinal approach: anatomic and clinical studies

Objective To investigate the feasibility and clinical application of the cervical pedicle screw fixation through intermuscular planes between musculus semispinalis cervicis and musculus semispinalis capitis. Methods Five adult specimens were selected for studying the anatomic features of musculus semispinalis cervicis and musculus semispinalis capitis and the distributions of surrounding deep cervical vassels and carotid nerve. Fifty cervical pedicle screws were placed into C3-C7 for all specimens. Besides, cervical transpedicular fixation with 49 screws was performed in 12 patients via the intermuscular planes between musculus semispinalis cervicis and musculus semispinalis capitis. Wounds and complications were detected after operation. Screw position was assessed by CT imaging. Results Musculus semispinalis capitis was the main part of the lateral intermuscular septum. Musculus semispinalis cervicis was the main part of the medial intermuscular septum. Multifidus and rotator participated in forming the cervical dorsal rami nerve bone fiber tube. Medial and lateral intermuscular tissues were dominated respectively by cervical dorsal medial branch and lateral branch. Deep cervical artery lied in upward branches between the semispinalis capitis and semispinalis cervicis, supplying both sides of the semispinalis. Six screws placed in the specimens cut through the pedicle wall. Screws were placed successfully in all the 12 patients. The plane between musculus semispinalis capitis and semispinalis cervicis could be separated easily. Four screws broke the pedicle wall, but there were no screw-related complications. Conclusions A new intermuscular plane through musculus semispinalis cervicis and musculus semispinalis capitis is developed to facilitate the low cervical pedicle screw insertion. Primary clinical results show cervical pedicle screw placement through the new approach is safe, feasible, easy and minimally invasive. Key words: Cervical vertebrae; Anatomy; Pedicle screws

0392 : AMPKα1 regulates cell adhesion and migration of human cardiac fibroblasts via cytoskeletal remodelling pathway

A key detrimental characteristic of left ventricular (LV) remodelling is fibrosis. The pathogenesis of cardiac fibrosis includes migration of cardiac fibroblasts. Remodelling of actin cytoskeleton is a hallmark of the migrating cells. AMP-activated protein kinase (AMPK) regulates actin cytoskeleton organization and has been shown to influence LV remodelling. In this study, we investigated whether A-769662, a pharmacological AMPK activator, modulates human cardiac fibroblast (HCF) migration and adhesion by affecting actin organization. Single-cell migration was assessed by time-lapse imaging. Focal adhesions (FA) were visualized by immunofluorescence together with fluorescent phalloidin to stain actin filaments. Phosphorylation state of myosin regulatory light chains (MLC) was determined by western blot analysis and immunofluorescent staining. RhoA activity was assessed using a pull down method. A-769662 significantly decreased HCF motility, in an AMPKα1- dependent manner. In addition, A-769662-treated cells shifted from an elongated shape, characterized by leading and trailing edges, to a more polygonal one with numerous and thicker stress cables, mainly dorsal fibres and transverse arcs. This was accompanied by markedly increased cell adhesion and focal adhesion size. Concomitantly, AMPKα1 activation also resulted in a sustained activation of RhoA that was associated with a significant increase in MLC phosphorylation and its colocalization with transverse arcs. We postulate that A-769662 counteracts HCF migration through an AMPK-dependent sustained activation of the RhoA/MLC pathway, promoting actin polymerization and contraction. Myosin II-generated tension into FA is expected to promote their maturation and subsequently alter migration.

The ventral fiber pathway for pantomime of object use

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently.Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory–motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells

How adherent and contractile systems coordinate to promote cell shape changes is unclear. Here, we define a counterbalanced adhesion/contraction model for cell shape control. Live-cell microscopy data showed a crucial role for a contractile meshwork at the top of the cell, which is composed of actin arcs and myosin IIA filaments. The contractile actin meshwork is organized like muscle sarcomeres, with repeating myosin II filaments separated by the actin bundling protein α-actinin, and is mechanically coupled to noncontractile dorsal actin fibers that run from top to bottom in the cell. When the meshwork contracts, it pulls the dorsal fibers away from the substrate. This pulling force is counterbalanced by the dorsal fibers' attachment to focal adhesions, causing the fibers to bend downward and flattening the cell. This model is likely to be relevant for understanding how cells configure themselves to complex surfaces, protrude into tight spaces, and generate three-dimensional forces on the growth substrate under both healthy and diseased conditions.

FHOD1 regulates stress fiber organization by controlling transversal arc and dorsal fiber dynamics

The formin FHOD1 (formin homology 2 domain containing protein 1) can act as a capping and bundling protein in vitro. In cells, active FHOD1 stimulates the formation of ventral stress fibers. However, the cellular mechanisms by which this phenotype is produced and the physiological relevance of FHOD1 function are not currently understood. Here, we first show that FHOD1 controls the formation of two distinct stress fiber precursors differentially. On the one hand, it inhibits dorsal fiber growth, which requires the polymerization of parallel bundles of long actin filaments. On the other hand, it stimulates transverse arcs that are formed by the fusion of short antiparallel actin filaments. This combined action is crucial for the maturation of stress fibers and their spatio-temporal organization, and a lack of FHOD1 function perturbs dynamic cell behavior during cell migration. Furthermore, we show that the GTPase-binding and formin homology 3 domains (GBD and FH3) are responsible for stress fiber association and colocalization with myosin. Surprisingly, a version of FHOD1 that lacks these domains nevertheless retains its full capacity to stimulate arc and ventral stress fiber formation. Based on our findings, we propose a mechanism in which FHOD1 promotes the formation of short actin filaments and transiently associates with transverse arcs, thus providing tight temporal and spatial control of the formation and turnover of transverse arcs into mature ventral stress fibers during dynamic cell behavior.

Chronic degeneration of dorsal raphe serotonergic neurons modulates cortical spreading depression: A possible pathophysiology of migraine

The vascular serotonergic system in the brain has been implicated in the pathophysiology of migraine, however, involvement of the serotonergic nervous system of the brain parenchyma in the pathophysiology remains unclear. To investigate whether the brain parenchymal serotonergic nervous system is involved in the etiology of migraine, we prepared an experimental model of migraine by generation of cortical spreading depression (SD), characterized by spreading of neuronal/glial membrane depolarization accompanied by temporal elevation of the cerebral blood flow (CBF) throughout the cerebral cortical hemisphere in rats, which underwent pharmacological treatment for degeneration of serotonergic neurons in the dorsal raphe nucleus. We show here that (1) significant degeneration of serotonergic neurons in the dorsal raphe nucleus and serotonergic fibers in the cerebral cortex was observed in treated rats, (2) spreading velocity of the CBF changes was significantly increased in these rats, and (3) calculated width of the depolarization wave was significantly extended in these rats. These results indicate that the dorsal raphe serotonergic neurons modulate cortical spreading depression and might be involved in migraine pathology via a similar mechanism.

Damage to ventral and dorsal language pathways in acute aphasia

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the ventral extreme capsule pathway.

Effects of excimer lamp irradiation on rat dorsal root ganglion nerve fibers: Implications for possible application to intractable pruritus

Effects of excimer lamp irradiation on rat dorsal root ganglion nerve fibers: Implications for possible application to intractable pruritus

Development of the dorsal ramus of the spinal nerve in the chick embryo: A close relationship between development and expression of guidance cues

The spinal nerve, which is composed of dorsal root ganglion (DRG) axons and spinal motor axons, divides into ventral and dorsal rami. Although the development of the ventral ramus has been examined in considerable detail, that of the dorsal ramus has not. Therefore, we first examined the spatial-temporal pattern of the dorsal ramus formation in the chick embryo, with special reference to the projection to the dermamyotome and its derivatives. Next, we focused on two guidance molecules, chick semaphorin 3A (SEMA3A) and fibroblast growth factor 8 (FGF8), because these are the best candidates as molecules for controlling the dorsal ramus formation. Using in situ hybridization and immunohistochemistry methods, we clearly showed a close relationship between the spatial-temporal expression of SEMA3A/FGF8 and the projection of dorsal ramus fibers to the dorsal muscles. We further examined the axonal response of motor and DRG neurons to SEMA3A and FGF8. We showed that motor axons responded to both SEMA3A-induced repulsion and FGF8-induced attraction. On the other hand, DRG axons responded to SEMA3A-induced repulsion but not to FGF8-induced attraction. These findings suggest that FGF8-induced attraction may guide early motor axons beneath the myotome and that SEMA3A-induced repulsion may prevent these early motor axons from entering the myotome. Our results also imply that the loss of SEMA3A expression in the dorsal muscles may lead to the gross projection of the dorsal ramus fibers into the dorsal muscles. Together, SEMA3A and FGF8 may contribute to the proper formation of the dorsal ramus.