Juan Martino

Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data.

Despite electrostimulation studies of the white matter pathways, supporting the role of the inferior fronto-occipital fasciculus (IFOF) in semantic processing, little is known about the precise anatomical course of this fascicle, especially regarding its exact cortical terminations. Here, in the lights of these new functional data, we dissected 14 post-mortem human hemispheres using the Klingler fiber dissection technique, to study the IFOF fibers and to identify their actual cortical terminations in the parietal, occipital and temporal lobes. We identified two different components of the IFOF: (i) a superficial and dorsal subcomponent, which connects the frontal lobe with the superior parietal lobe and the posterior portion of the superior and middle occipital gyri, (ii) a deep and ventral subcomponent, which connects the frontal lobe with the posterior portion of the inferior occipital gyrus and the posterior temporo-basal area. Thus, our results are in line with the hypothesis of the functional role of the IFOF in the semantic system, by showing that it is mainly connected with two areas involved in semantics: the occipital associative extrastriate cortex and the temporo-basal region. Further combined anatomical (dissection and Diffusion Tensor Imaging) and functional (intraoperative subcortical stimulation) studies are needed, to clarify the exact participation of each IFOF subcomponent in semantic processing.

Analysis of the subcomponents and cortical terminations of the perisylvian superior longitudinal fasciculus: a fiber dissection and DTI tractography study

The anatomy of the perisylvian component of the superior longitudinal fasciculus (SLF) has recently been reviewed by numerous diffusion tensor imaging tractography (DTI) studies. However, little is known about the exact cortical terminations of this tract. The aim of the present work is to isolate the different subcomponents of this tract with fiber dissection and DTI tractography, and to identify the exact cortical connections. Twelve postmortem human hemispheres (6 right and 6 left) were dissected using the cortex-sparing fiber dissection. In addition, three healthy brains were analyzed using DTI-based tractography software. The different components of the perisylvian SLF were isolated and the fibers were followed until the cortical terminations. Three segments of the perisylvian SLF were identified: (1) anterior segment, connecting the supramarginal gyrus and superior temporal gyrus with the precentral gyrus, (2) posterior segment, connecting the posterior portion of the middle temporal gyrus with the angular gyrus, and (3) long segment of the arcuate fasciculus that connects the middle and inferior temporal gyri with the precentral gyrus and posterior portion of the inferior and middle frontal gyri. In the present study, three different components of the perisylvian SLF were identified. For the first time, our dissections revealed that each component was connected to a specific cortical area within the frontal, parietal and temporal lobes. By accurately depicting not only the trajectory but also cortical connections of this bundle, it is possible to develop new insights into the putative functional role of this tract.

Resting Functional Connectivity in Patients with Brain Tumors in Eloquent Areas

Resection of brain tumors adjacent to eloquent areas represents a challenge in neurosurgery. If maximal resection is desired without inducing postoperative neurological deficits, a detailed knowledge of the functional topography in and around the tumor is crucial. The aim of the present work is to evaluate the value of preoperative magnetoencephalography (MEG) imaging of functional connectivity to predict the results of intraoperative electrical stimulation (IES) mapping, the clinical gold standard for neurosurgical localization of functional areas.

Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain

Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. ‘cortex‐sparing fiber dissection’. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex‐sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)‐based tractography software. DTI fiber tract reconstructions were compared with cortex‐sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto‐occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo‐basal cortex. The UF crosses the limen insulae and connects the orbito‐frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex‐sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research.

New insights into the anatomic dissection of the temporal stem with special emphasis on the inferior fronto-occipital fasciculus: implications in surgical approach to left mesiotemporal and temporoinsular structures.

OBJECTIVE To analyze the 3-dimensional relationships of the inferior fronto-occipital fasciculus (IFOF) within the temporal stem using anatomic dissection and to study the surgical application. METHODS Ten postmortem human hemispheres (5 right, 5 left) were dissected using the Klingler fiber dissection technique. The 3-dimensional relationships of the IFOF with different landmarks of the temporal stem, insula, and temporal lobe were analyzed and measured. RESULTS An average distance of 10.9 mm (range, 8–15 mm) was observed between the limen insulae and the anterior edge of the IFOF under the inferior limiting sulcus of the insula. This anterior one-third of the temporal stem is crossed by the uncinate fasciculus. The IFOF crosses the posterior two-thirds of the temporal stem, in the space between the posterior limit of the uncinate fasciculus and the lateral geniculate body. The average superoinferior distance between the IFOF and the inferior limiting sulcus was 3.8 mm. The auditory radiations and the claustro-opercular and insulo-opercular fibers of the external and extreme capsules pass through the temporal stem above the IFOF, whereas the optic radiations pass below. CONCLUSION In the transsylvian approach to the mesiotemporal structures in the left dominant hemisphere, an incision within the posterior 8 mm from the limen insulae is less likely to damage the IFOF than more posterior incisions along the inferior limiting sulcus. In the temporal transopercular approach to left temporo-insular gliomas, the IFOF constitutes the deep functional limit of the resection within the temporal stem.

White matter connections of the supplementary motor area in humans

Introduction The supplementary motor area (SMA) is frequently involved by brain tumours (particularly WHO grade II gliomas). Surgery in this area can be followed by the ‘SMA syndrome’, characterised by contralateral akinesia and mutism. Knowledge of the connections of the SMA can provide new insights on the genesis of the SMA syndrome, and a better understanding of the challenges related to operating in this region. Methods White matter connections of the SMA were studied with both postmortem dissection and advance diffusion imaging tractography. Postmortem dissections were performed according to the Klingler technique. 12 specimens were fixed in 10% formalin and frozen at −15°C for 2 weeks. After thawing, dissection was performed with blunt dissectors. For diffusion tractography, high-resolution diffusion imaging datasets from 10 adult healthy controls from the Human Connectome Project database were used. Whole brain tractography was performed using a spherical deconvolution approach. Results Five main connections were identified in both postmortem dissections and tractography reconstructions: (1) U-fibres running in the precentral sulcus, connecting the precentral gyrus and the SMA; (2) U-fibres running in the cingulate sulcus, connecting the SMA with the cingulate gyrus; (3) frontal ‘aslant’ fascicle, directly connecting the SMA with the pars opercularis of the inferior frontal gyrus; (4) medial fibres connecting the SMA with the striatum; and (5) SMA callosal fibres. Good concordance was observed between postmortem dissections and diffusion tractography. Conclusions The SMA shows a wide range of white matter connections with motor, language and lymbic areas. Features of the SMA syndrome (akinesia and mutism) can be better understood on the basis of these findings.

Subcortical anatomy of the lateral association fascicles of the brain: A review.

Precise knowledge of the connectivities of the different white matter bundles is of great value for neuroscience research. Our knowledge of subcortical anatomy has improved exponentially during recent decades owing to the development of magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI tractography has led to important progress in understanding white matter anatomy, the precise trajectory and cortical connections of the subcortical bundles remain poorly determined. The recent literature was extensively reviewed in order to analyze the trajectories and cortical terminations of the lateral association fibers of the brain.The anatomy of the following tracts is reviewed: superior longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, uncinate fasciculus, frontal aslant tract, and vertical occipital fasciculus. The functional role of a tract can be inferred from its topography within the brain. Knowing the functional roles of the cortical areas connected by a certain bundle, it is possible to develop new insights into the putative functional properties of such connections. Clin. Anat. 563–569, 2014.

Magnetoencephalographic imaging of resting-state functional connectivity predicts postsurgical neurological outcome in brain gliomas.

BACKGROUND The removal of brain tumors in perieloquent or eloquent cortex risks causing new neurological deficits in patients. The assessment of the functionality of perilesional tissue is essential to avoid postoperative neurological morbidity. OBJECTIVE To evaluate preoperative magnetoencephalography-based functional connectivity as a predictor of short- and medium-term neurological outcome after removal of gliomas in perieloquent and eloquent areas. METHODS Resting-state whole-brain magnetoencephalography recordings were obtained from 79 consecutive subjects with focal brain gliomas near or within motor, sensory, or language areas. Neural activity was estimated using adaptive spatial filtering. The mean imaginary coherence between voxels in and around brain tumors was compared with contralesional voxels and used as an index of their functional connectivity with the rest of the brain. The connectivity values of the tissue resected during surgery were correlated with the early (1 week postoperatively) and medium-term (6 months postoperatively) neurological morbidity. RESULTS Patients undergoing resection of tumors with decreased functional connectivity had a 29% rate of a new neurological deficit 1 week after surgery and a 0% rate at 6-month follow-up. Patients undergoing resection of tumors with increased functional connectivity had a 60% rate of a new deficit at 1 week and a 25% rate at 6 months. CONCLUSION Magnetoencephalography connectivity analysis gives a valuable preoperative evaluation of the functionality of the tissue surrounding tumors in perieloquent and eloquent areas. These data may be used to optimize preoperative patient counseling and surgical strategy.

Morbidity profile following aggressive resection of parietal lobe gliomas

OBJECT The impact of parietal lobe gliomas is typically studied in the context of parietal lobe syndromes. However, critical language pathways traverse the parietal lobe and are susceptible during tumor resection. The authors of this study reviewed their experience with parietal gliomas to characterize the impact of resection and the morbidity associated with language. METHODS The study population included adults who had undergone resection of parietal gliomas of all grades. Tumor location was identified according to a proposed classification system for parietal region gliomas. Low- and high-grade tumors were volumetrically analyzed using FLAIR and T1-weighted contrast-enhanced MR imaging. RESULTS One hundred nineteen patients with parietal gliomas were identified--34 with low-grade gliomas and 85 with high-grade gliomas. The median patient age was 45 years, and most patients (53) presented with seizures, whereas only 4 patients had an appreciable parietal lobe syndrome. The median preoperative tumor volume was 31.3 cm(3), the median extent of resection was 96%, and the median postoperative tumor volume was 0.9 cm(3). Surprisingly, the most common early postoperative neurological deficit was dysphasia (16 patients), not weakness (12 patients), sensory deficits (14 patients), or parietal lobe syndrome (10 patients). A proposed parietal glioma classification system, based on surgical anatomy, was predictive of language deficits. CONCLUSIONS This is the largest reported experience with parietal lobe gliomas. The findings suggested that parietal language pathways are compromised at a surprisingly high rate. The proposed parietal glioma classification system is predictive of postoperative morbidity associated with language and can assist with preoperative planning. Taken together, these data emphasize the value of identifying language pathways when operating within the parietal lobe.

Cellular Plasticity Confers Migratory and Invasive Advantages to a Population of Glioblastoma‐Initiating Cells that Infiltrate Peritumoral Tissue

Glioblastoma (GBM) is associated with infiltration of peritumoral (PT) parenchyma by isolated tumor cells that leads to tumor regrowth. Recently, GBM stem‐like or initiating cells (GICs) have been identified in the PT area, but whether these GICs have enhanced migratory and invasive capabilities compared with GICs from the tumor mass (TM) is presently unknown. We isolated GICs from the infiltrated PT tissue and the TM of three patients and found that PT cells have an advantage over TM cells in two‐dimensional and three‐dimensional migration and invasion assays. Interestingly, PT cells display a high plasticity in protrusion formation and cell shape and their migration is insensitive to substrate stiffness, which represent advantages to infiltrate microenvironments of different rigidity. Furthermore, mouse and chicken embryo xenografts revealed that only PT cells showed a dispersed distribution pattern, closely associated to blood vessels. Consistent with cellular plasticity, simultaneous Rac and RhoA activation are required for the enhanced invasive capacity of PT cells. Moreover, Rho GTPase signaling modulators αVβ3 and p27 play key roles in GIC invasiveness. Of note, p27 is upregulated in TM cells and inhibits RhoA activity. Gene silencing of p27 increased the invasive capacity of TM GICs. Additionally, β3 integrin is upregulated in PT cells. Blockade of dimeric integrin αVβ3, a Rac activator, reduced the invasive capacity of PT GICs in vitro and abrogated the spreading of PT cells into chicken embryos. Thus, our results describe the invasive features acquired by a unique subpopulation of GICs that infiltrate neighboring tissue. STEM Cells 2013;31:1075–1085