Developmental changes and injury induced disruption of the radial organization of the cortex in the immature rat brain revealed by in vivo diffusion tensor MRI

During brain development, morphological changes modify the cortex from its immature radial organization to its mature laminar appearance. Applying in vivo diffusion tensor imaging (DTI), the microstructural organization of the cortex in the immature rat was analyzed and correlated to neurohistopathology. Significant differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were detected between the external (I-III) and deep (IV-VI) cortical layers in postnatal day 3 (P3) and P6 pups. With cortical maturation, ADC was reduced in both cortical regions, whereas a decrease in FA was only seen in the deep layers. A distinct radial organization of the external cortical layers with the eigenvectors perpendicular to the pial surface was observed at both ages. Histology revealed maturational differences in the cortical architecture with increased neurodendritic density and reduction in the radial glia scaffolding. Early DTI after hypoxia-ischemia at P3 shows reduced ADC and FA in the ipsilateral cortex that persisted at P6. Cortical DTI eigenvector maps reveal microstructural disruption of the radial organization corresponding to regions of neuronal death, radial glial disruption, and astrocytosis. Thus, the combined use of in vivo DTI and histopathology can assist in delineating normal developmental changes and postinjury modifications in the immature rodent brain.     

脑部高分辨率扩散张量成像研究进展

扩散张量成像(DTI)通过活体组织中水分子的扩散运动描述组织结构变化,基于该技术的脑白质纤维追踪技术能够无创、清晰显示脑神经纤维的解剖结构,对于诊断和治疗脑部疾病具有重要价值。扩散张量模型基于高斯分布假设,在纤维交叉区域无法指明纤维方向,为此提出了高分辨率DTI。本文对基于高分辨率DTI的神经纤维追踪技术的研究进展进行综述。     

Predicting functional cortical ROIs via DTI-derived fiber shape models

Studying structural and functional connectivities of human cerebral cortex has drawn significant interest and effort recently. A fundamental and challenging problem arises when attempting to measure the structural and/or functional connectivities of specific cortical networks: how to identify and localize the best possible regions of interests (ROIs) on the cortex? In our view, the major challenges come from uncertainties in ROI boundary definition, the remarkable structural and functional variability across individuals and high nonlinearities within and around ROIs. In this paper, we present a novel ROI prediction framework that localizes ROIs in individual brains based on their learned fiber shape models from multimodal task-based functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data. In the training stage, shape models of white matter fibers are learnt from those emanating from the functional ROIs, which are activated brain regions detected from task-based fMRI data. In the prediction stage, functional ROIs are predicted in individual brains based only on DTI data. Our experiment results show that the average ROI prediction error is around 3.94 mm, in comparison with benchmark data provided by working memory and visual task-based fMRI. Our work demonstrated that fiber bundle shape models derived from DTI data are good predictors of functional cortical ROIs.     

Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography

The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a "small-world" architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.     

Diffusion tensor imaging of benign intracranial hypertension: absence of cerebral oedema

Cerebral oedema, it has been suggested, may have a role in the pathophysiology of benign intracranial hypertension (BIH). We applied diffusion tensor MR imaging (DTI), a technique able to detect cerebral oedema, to the study of patients with BIH. A quantitative regional analysis of diffusion parameters (trace and relative anisotropy) was conducted by comparing five BIH patients and six healthy controls. A small but significant increase in anisotropy accompanied by a small but significant decrease in trace was found in the putamen and head of the caudate nucleus. No significant changes were demonstrated in the thalamus, cerebral white matter or cortical regions. Our findings support other recent work that suggests cerebral oedema is not a factor in the pathogenesis of BIH.     

Developmental Changes Revealed by Immunohistochemical Markers in Human Cerebral Cortex

The developing human cerebral cortex is distinguished by a particularlywide subplate, a transient zone in which crucial cell-cell interactionsoccur. To further understand the role of the subplate in humanbrain development, we have studied the immunohistochemical expressionof certain neuronal (GAP-43, MAP-2 parvalbumin) and astroglial(vimentin, GFAP} markers in the developing visual cortex fromgestational ages of 14 weeks to 9 months post-term. At 14–22weeks, immunoreactivity to GAP-43, a protein involved in axonaloutgrowth, was most prominent in the subplate and marginal zoneneuropil and in the fibers of the radiations running near theventricular zone; at 22–42 weeks, GAP-43 immunoreactivefibers were observed in the maturing cortical plate. Immunoreactivityfor the microtubule-associated protein MAP-2 was present inthe differentiating cortical plate at 14 weeks, but at 22–42weeks was most prominent in the somata and dendrites of differentiatedneurons, particularly the Cajal-Retzius neurons of the marginalzone, in neurons of the subplate and in those forming corticallayer 5. Parvalbumin immunoreactivity did not appear until 26weeks, when stained neurons were in a sparse band of cells inlayer 6 and upper subplate. Vimentin and GFAP did not staindifferentiated neuronal cells. Vimentin immunoreactivity appearedearly in neuroepithelial and radial glial cells, decreasingafter 35 weeks, with a concomitant increase in GFAP immunoreactivityin radial glial and maturing astrocytic cells. Our results showthat despite the greater complexity of the developing humanneocortex, molecular markers are expressed in spatial and temporalpatterns similar to those observed in non-human primates, carnivoresand rodents. These protein markers should prove useful in developmentalstaging, and in providing a framework in which to examine congenitaldisorders of cerebral development.     

Laminar organization of the human fetal cerebrum revealed by histochemical markers and magnetic resonance imaging

The developing human cerebrum displays age-specific changes in its patterns of lamination. Among these, the subplate zone is the most prominent transient compartment because growing major afferent systems temporarily reside in this zone, establish synapses and take part in cellular interactions that are crucial for subsequent cortical development. We explored the potential of magnetic resonance imaging (MRI) for tracing the developmental history of the most prominent cortical layer (the subplate zone) and other laminar compartments of the fetal cerebral wall between 15 and 36 weeks post-ovulation. We found that changes in the MRI lamination pattern of the human fetal cerebral wall are predominantly caused by changes in the subplate zone. Histochemical staining of the extracellular matrix (ECM) enables selective visualization of the subplate zone and correlation with an increase in MRI signal intensity in the subplate zone and ingrowth and accumulation of thalamocortical and corticocortical afferents and their subsequent relocation to the cortical plate. Thus, dynamic changes in the MRI appearance of the subplate zone and histochemical staining of its ECM can be used as indirect parameters for an assessment of normal versus disturbed unfolding of crucial histogenetic events that are involved in prenatal shaping of the human cerebral cortex.     

Synaptogenesis in layer I of the human cerebral cortex in the first half of gestation

The formation of synapses is among the most important steps in neuronal differentiation and the establishment of neuronal circuits. To establish baseline data about the time of onset, density and the course of synaptic formation in different regions of the human cerebral cortex before birth, synaptogenesis in layer I was examined by electron microscopy in fetuses ranging in age from 6 to 24 gestational weeks. Synapses were first observed in the primordial plexiform layer (marginal zone) in both the lateral and medial cerebral walls between the 6th and 7th gestational week, before the formation of the cortical plate. The density of synapses increased rapidly after the formation of the cortical plate, increasing by 37% between 12 and 14 weeks. Synaptogenesis proceeded at the same rate in the lateral and occipital cortex during this period. Further, with one exception, the insular region, synaptic density was comparable in prospective areas of prefrontal, motor, visual, temporal and cingulate cortex in a group of fetuses at midgestation (20 weeks). The results are consistent with a synchronous course of synaptogenesis of the neocortex.      

3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum

Studies in non-human primates have shown that medial premotorprojections to the striatum are characterized as a set of distinctcircuits conveying different type of information. This studyassesses the anatomical projections from the supplementary motorarea (SMA), pre-SMA and motor cortex (MC) to the human striatumusing diffusion tensor imaging (DTI) axonal tracking. Eightright-handed volunteers were studied at 1.5 T using DTI axonaltracking. A connectivity matrix was computed, which tested forconnections between cortical areas (MC, SMA and pre-SMA) andsubcortical areas (posterior, middle and anterior putamen andthe head of the caudate nucleus) in each hemisphere. Pre-SMAprojections to the striatum were located rostral to SMA projectionsto the striatum. The SMA and the MC were similarly connectedto the posterior and middle putamen and not to the anteriorstriatum. These data show that the MC and SMA have connectionswith similar parts of the sensorimotor compartment of the humanstriatum, whereas the pre-SMA sends connections to more rostralparts of the striatum, including the associative compartment.     

Error-related negativity is mediated by fractional anisotropy in the posterior cingulate gyrus--a study combining diffusion tensor imaging and electrophysiology in healthy adults

White matter (WM) is critical to cognitive function and brain activity. The objective of the present study was to test whether diffusion tensor imaging (DTI) derived WM measures are related to the cognitive event-related potential error-related negativity (ERN). Eighty-seven healthy middle-aged adults underwent DTI scanning and electrophysiological recordings while doing a version of the Eriksen flanker task. ERN was elicited in error trials. Fractional anisotropy (FA) was calculated based on the DTI scans. FA indexes degree of anisotropic diffusion in every voxel, and is assumed related to the integrity of myelinated fiber bundles. The principal neuronal generator for ERN is located in the anterior cingulate cortex (ACC). Hence, the relationship between FA in the cingulum bundle and ERN amplitude was tested. It was found that FA in the left posterior cingulate correlated with ERN. Eigenvalue analyses revealed that radial diffusivity was responsible for the FA effect. ERN amplitude predicted response accuracy in the Flanker task, suggesting that electrophysiological measures are intermediate explanatory variables connecting DTI indices of WM organization, synchronization of large cell assemblies, and behavior.     

Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury

A debilitating consequence of complete spinal cord injury (SCI)is the loss of motor control. Although the goal of most SCItreatments is to re-establish neural connections, a potentialcomplication in restoring motor function is that SCI may resultin anatomical and functional changes in brain areas controllingmotor output. Some animal investigations show cell death inthe primary motor cortex following SCI, but similar anatomicalchanges in humans are not yet established. The aim of this investigationwas to use voxel-based morphometry (VBM) and diffusion tensorimaging (DTI) to determine if SCI in humans results in anatomicalchanges within motor cortices and descending motor pathways.Using VBM, we found significantly lower gray matter volume incomplete SCI subjects compared with controls in the primarymotor cortex, the medial prefrontal, and adjacent anterior cingulatecortices. DTI analysis revealed structural abnormalities inthe same areas with reduced gray matter volume and in the superiorcerebellar cortex. In addition, tractography revealed structuralabnormalities in the corticospinal and corticopontine tractsof the SCI subjects. In conclusion, human subjects with completeSCI show structural changes in cortical motor regions and descendingmotor tracts, and these brain anatomical changes may limit motorrecovery following SCI.     

Neonatal NMDA receptor blockade disturbs neuronal migration in rat somatosensory cortex in vivo

Glutamate plays an important role in the control of neuronal migration in the developing cerebral cortex. The present study describes changes in the structure and function of the cerebral cortex after transient blockade of N-methyl-D-aspartate (NMDA) receptors during the late period of neuronal migration. Elvax slices containing the NMDA antagonist MK801 were placed over the somatosensory cortex of newborn rats and the drug was released over a period of 2-3 days. After survival times of 1 or 2 weeks, neuroanatomical and in vitro electrophysiological analyses revealed prominent structural and functional alterations in the cortical region underlying the implant. Cortical lamination was disturbed and heterotopic cell clusters were found in layer I of MK801-treated animals. Morphologically identified pyramidal neurons recorded in MK801-treated cortex revealed late NMDA receptor-mediated synaptic inputs and fragile monosynaptic responses at stimulation frequencies >0.2 Hz. Our data indicate that impairment of NMDA receptors during early corticogenesis induces neuronal migration disorders and delays the functional maturation of the developing cortical network.     

Preoperative and intraoperative brain mapping for the resection of eloquent-area tumors. A prospective analysis of methodology, correlation, and usefulness based on clinical outcomes

Background

Localization of brain function is a fundamental requisite for the resection of eloquent-area brain tumors. Preoperative functional neuroimaging and diffusion tensor imaging can display cortical functional organization and subcortical anatomy of major white matter bundles. Direct cortical and subcortical stimulation is widely used in routine practice, however, because of its ability to reveal tissue function in eloquent regions. The role and integration of these techniques is still a matter of debate. The objective of this study was to assess surgical and functional neurological outputs of awake surgery and intraoperative cortical and subcortical electrical stimulation (CSES) and to use CSES to examine the reliability of preoperative functional magnetic resonance (fMRI) and diffusion tensor imaging fiber tracking (DTI-FT) for surgical planning.

Patients and methods

We prospectively studied 27 patients with eloquent-area tumors who were selected to undergo awake surgery and direct brain mapping. All subjects underwent preoperative sensorimotor and language fMRI and DTI tractography of major white matter bundles. Intra- and postoperative complications, stimulation effects, extent of resection, and neurological outcome were determined. We topographically correlated intraoperatively identified sites (cortical and subcortical) with areas of fMRI activation and DTI tractography.

Results

Total plus subtotal resection reached 88.8%. Twenty-one patients (77.7%) suffered transient postoperative worsening, but at 6 months follow-up only three (11.1%) patients had persistent neurological impairment. Sensorimotor cortex direct mapping correlated 92.3% with fMRI activation, while direct mapping of language cortex correlated 42.8%. DTI fiber tracking underestimated the presence of functional fibers surrounding or inside the tumor.

Conclusion

Preoperative brain mapping is useful when planning awake surgery to estimate the relationship between the tumor and functional brain regions. However, these techniques cannot directly lead the surgeon during resection. Intraoperative brain mapping is necessary for safe and maximal resection and to guarantee a satisfying neurological outcome. This multimodal approach is more aggressive, leads to better outcomes, and should be used routinely for resection of lesions in eloquent brain regions.     

Diffusion tensor imaging in hydrocephalus-findings before and after shunt surgery

Background  

To evaluate changes in diffusion tensor imaging (DTI)-derived parameters in patients with hydrocephalus (HC) before and several weeks after shunt surgery.     

Dissociated pathways for successful memory retrieval from the human parietal cortex: anatomical and functional connectivity analyses

The parietal cortex has traditionally been implicated in spatial attention and eye-movement processes. Recent functional neuroimaging studies have found that activation in the parietal cortex is related to successful recognition memory. The activated regions consistently include the intraparietal sulcus in the lateral parietal cortex and the precuneus in the medial parietal cortex. However, little is known about the functional differences between lateral and medial parietal cortices in the memory retrieval process. In this study, we examined whether the human lateral and medial parietal lobes have differential anatomical and functional connectivity with the temporal lobe. To this end, we used functional magnetic resonance imaging to constrain the analysis of anatomical connectivity obtained by diffusion tensor imaging (DTI). Both DTI tractography and functional connectivity analysis showed that the lateral parietal region has anatomical and functional connections with the lateral temporal lobe, and the medial parietal region has connections with the medial temporal lobe. These results suggest the existence of segregated lateral and medial parieto-temporal pathways in successful memory retrieval.     

Morphological alteration and reduction of MAP2-immunoreactivity in pyramidal neurons of cerebral cortex in a rat model of focal cortical compression

Subdural hematoma causes cortical damage including brain tissue disruption, often resulting in neuronal dysfunction and neurological impairment. The aim of the present study was to identify the relationship between cerebral compression and neuronal injury. In this report, we investigated time-dependent morphological alterations within layers II, III, and V pyramidal neurons in the cerebral cortex, using Golgi-Cox staining and immunohistochemistry for microtubule-associated protein 2 (MAP2) in a rat model of focal cortical compression. An acryl pole was used to experimentally induce chronic cerebral compression by continuous pressure on the cortical surface. Changes in cellular morphology were examined at five survival time periods: 12?h and 1, 2, 3, and 4 weeks. The Golgi-Cox method revealed time-dependent alterations in dendritic length of apical and basilar dendrites of pyramidal neurons. The number of dendritic branch segments and spines of basilar dendrites were decreased in cells in layers II, III, and V. Immunohistochemical staining for MAP2 revealed changes in the intracellular distribution of immunoreactive materials. A significant reduction in MAP2 immunostaining was found in nerve cell bodies and apical dendrites of ipsilateral cortical neurons. The number of MAP2-immunoreactive neurons was significantly decreased at 12?h compared with the contralateral cerebral cortex in the same animal. Dendritic changes in layers II, III, and V pyramidal neurons were accompanied by reductions in intracellular MAP2-immunoreactive materials. The present results suggest that cortical compression causes alteration of cellular morphology as a consequence of injury, and that these morphological changes may be related to reductions in MAP2-immunoreactive materials.     

Virtual reality presurgical planning for cerebral gliomas adjacent to motor pathways in an integrated 3-D stereoscopic visualization of structural MRI and DTI tractography

Objective  

Resection of gliomas invading primary motor cortex and subcortical motor pathway is difficult in both surgical decision-making and functional outcome prediction. In this study, magnetic resonance (MR) diffusion tensor imaging (DTI) data were used to perform tractography to visualize pyramidal tract (PT) along its whole length in a stereoscopic virtual reality (VR) environment. The potential value of its clinical application was evaluated.     

Function and connectivity in human primary auditory cortex: a combined fMRI and DTI study at 3 Tesla

Human primary auditory cortex (PAC) is functionally organized in a tonotopic manner. Past studies have used neuroimaging to characterize tonotopic organization in PAC and found similar organization as that described in mammals. In contrast to what is known about PAC in primates and nonprimates, in humans, the structural connectivity within PAC has not been defined. In this study, stroboscopic event-related functional magnetic resonance imaging (fMRI) was utilized to reveal mirror symmetric tonotopic organization consisting of a high-low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography and probabilistic mapping was used to study projection patterns within tonotopic areas. Based on earlier physiological and histological work in nonhuman PAC, we hypothesized the existence of cross-field isofrequency (homotopic) and within-field non-isofrequency (heterotopic)-specific axonal projections in human PAC. The presence of both projections types was found in all subjects. Specifically, the number of diffusion tensor imaging (DTI) reconstructed fibers projecting between high- and low-frequency regions was greater than those fibers projecting between 2 high-frequency areas, the latter of which are located in distinct auditory fields. The fMRI and DTI results indicate that functional and structural properties within early stages of the auditory processing stream are preserved across multiple mammalian species at distinct evolutionary levels.     

The early differentiation of the neocortex: a hypothesis on neocortical evolution.

During development, a cerebral cortex appears in the wall of the telencephalic vesicle in reptiles and mammals. It arises from a cell-dense cortical plate, which develops within a primordial preplate. The neurons of the preplate are essential for cortical development; they regulate the neuronal migration of the cortical plate neurons and form the first axonal connections. In the reptilian cortex and in the hippocampus of the mammalian cerebral cortex, most ingrowing afferent axons run above the cortical plate, in the zone where the receptive tufts of apical dendrites of the cortical pyramidal neurons branch extensively. In the mammalian neocortex, however, axons enter mainly from below the cortical plate where they do not encounter the apical tufts of these pyramidal neurons. In this paper, we discuss the idea that this difference in cortical development has relieved a functional constraint in the expansion of the cortex during evolution. We hypothesize that the entrance of axons below the cell-dense cortical plate, together with the inside-out migration of cortical neurons, ensures that the neocortex remains an "open" system, able to differentiate into new (sub)layers and more cortical areas.     

Cerebral Cortical Progenitors Are Fated to Produce Region-specific Neuronal Populations

The mammalian cerebral cortex is characterized by its organizationinto anatomically and functionally discrete regions. Duringcortical development, a homogeneousappearing population of cellsalong the ventricular surface generates the neurons and gliathat ultimately form these cytoarchitectonic areas. The limbicsystem-associated membrane protein (LAMP) is a neuronal, cellsurface glycoprotein that identifies neurons restricted to limbiccerebral cortical areas (Levitt, 1984). LAMP is expressed earlyin development (Horton and Levitt, 1988), and transplantationstudies in the rat suggest that cells in the cerebral wall arecommitted to a limbic or nonlimbic molecular phenotype by embryonicday 14 (E14) (Barbe and Levitt, 1991). However, at E12, cellsdestined for the cerebral cortex are still multipotential andpresumably depend on local, extrinsic signals to adopt a limbicphenotype. We have developed an in vitro assay system for examiningthe fate of these multipotential progenitors and identifyingpotential environmental regulators of neuronal differentiation.Regions of the lateral (limbic) and dorsal (nonlimbic) cerebralwall at E12 are dissected, dissociated, and grown in low-densitycultures in defined medium. The cells are examined by immunocytochemistryfor expression of MAP2, a neuronal cytoskeletal protein, andLAMP to define neuronal differentiation and the expression ofa limbic molecular phenotype, respectively. We find that after4 d in culture, up to 75% of the progenitor cells from presumptivelimbic cortex express LAMP upon differentiation. In contrast,only 20–30% of the differentiated cells from presumptivesensorimotor cortex express LAMP. Thus, most cortical progenitorsare fated to a limbic or nonlimbic phenotype early in development,and the decision by neuronal stem cells to differentiate intoneurons exhibiting this molecular phenotype occurs prior tothe completion of neurogenesis, in the absence of subcorticalenvironmental cues.