Paraffin embedding of the whole human cerebral hemisphere to assess arterial distribution territories.

Commonly used to decode the human brain's structural complexity, ex vivo dissection focuses on a given structure or region but cannot depict the whole brain organization (for example, its arterial distribution territories). Where dissection reaches its limit, the combination of tissue sectioning and 3D reconstruction may provide a volume for the assessment of structures from any view angle, following them dynamically to understand their spatial relationships. However, to produce sections, standard histological tissue processing protocols for paraffin embedding cannot be applied to a cerebral hemisphere as the latter is extensively larger than the conventional specimens. This paper presents a protocol for paraffin embedding of the whole human cerebral hemisphere and a method to reconstruct 3D volumes from serially sectioned and photographed paraffin blocks containing embedded hemispheres. Seven ex vivo whole human cerebral hemispheres were included, two were serially sectioned. Main cerebral arteries were injected with colored media to label arterial territories. A detailed description of every step, from tissue processing to image acquisition of cut blockfaces and volume reconstruction, is provided. Tissue processing and section cutting were reproducible, and the former provided complete and homogeneous paraffin wax impregnation. 3D visualization of the reconstructed whole human cerebral hemisphere successfully showed the distribution territories of the main cerebral arteries. In addition, we discuss the challenges we faced and overcame while developing the presented method and highlight its originality.

Frontal trans opercular approaches to the insula: building the mental picture from procedure-guided anatomical dissection.

BACKGROUND: Performing transopercular frontal approaches to the insula, widely used in glioma surgeries, necessitates a meticulous understanding of both cortical and subcortical neuroanatomy. This precision is vital for preserving essential structures and accurately interpreting the results of direct electrical stimulation. Nevertheless, acquiring a compelling mental image of the anatomy of this region can be challenging due to several factors, among which stand out its complexity and the fact that white matter fasciculi are imperceptible to the naked eye in the living brain. AIM: In an effort to optimize the study of the anatomy relevant to this topic, we performed a procedure-guided laboratory study using subpial dissection, fiber dissection, vascular coloration, and stereoscopic photography in a "real-life" surgical perspective. METHODS: Nine cerebral specimens obtained from body donation were extracted and fixed in formalin. Colored silicone injection and a variant of Klinglers's technique were used to demonstrate vascular and white matter structures, respectively. We dissected and photographed the specimens in a supero-antero-lateral view to reproduce the surgeon's viewpoint. The anatomy related to the development of the surgical corridor and resection cavity was documented using both standard photography and the red-cyan anaglyph technique. RESULTS: The anatomy of frontal transopercular approaches to the insula involved elements of different natures-leptomeningeal, cortical, vascular, and fascicular-combining in the surgical field in a complex disposition. The disposition of these structures was successfully demonstrated through the aforementioned anatomical techniques. Among the main structures in or around the surgical corridor, the orbital, triangular, and opercular portions of the inferior frontal gyrus are critical landmarks in the cortical stage, as well as the leptomeninges of the Sylvian fissure and the M2-M4 branches of the middle cerebral artery in the subpial dissection stage, and the inferior fronto-occipital, uncinate and arcuate fasciculi, and the corona radiata in establishing the deep limits of resection. CONCLUSIONS: Procedure-guided study of cerebral hemispheres associating subpial, vascular, and fiber dissection from a surgical standpoint is a powerful tool for the realistic study of the surgical anatomy relevant to frontal transopercular approaches to the insula.

Doing more with less: Realistic stereoscopic three-dimensional anatomical modeling from smartphone photogrammetry.

Traditional teaching methods struggle to convey three-dimensional concepts effectively. While 3D virtual models and virtual reality platforms offer a promising approach to teaching anatomy, their cost and specialized equipment pose limitations, especially in disadvantaged areas. A simpler alternative is to use virtual 3D models displayed on regular screens, but they lack immersion, realism, and stereoscopic vision. To address these challenges, we developed an affordable method utilizing smartphone-based 360° photogrammetry, virtual camera recording, and stereoscopic display (anaglyph or side-by-side technique). In this study, we assessed the feasibility of this method by subjecting it to various specimen types: osteological, soft organ, neuroanatomical, regional dissection, and a dedicated 3D-printed testing phantom. The results demonstrate that the 3D models obtained feature a complete mesh with a high level of detail and a realistic texture. Mesh and texture resolutions were estimated to be approximately 1 and 0.2 mm, respectively. Additionally, stereoscopic animations were both feasible and effective in enhancing depth perception. The simplicity and affordability of this method position it as a technique of choice for creating easily photorealistic anatomical models combined with stereoscopic depth visualization.

Direct Inside-Out Observation of Superficial White Matter Fasciculi in the Human Brain.

Background: Recent methodological advances in the study of the cerebral white matter have left short association fibers relatively underexplored due to their compact and juxtacortical nature, which represent significant challenges for both post-mortem post-cortex removal dissection and magnetic resonance-based diffusion imaging. Objective: To introduce a novel inside-out post-mortem fiber dissection technique to assess short association fiber anatomy. Methods: Six cerebral specimens were obtained from a body donation program and underwent fixation in formalin. Following two freezing and thawing cycles, a standardized protocol involving peeling fibers from deep structures towards the cortex was developed. Results: The inside-out technique effectively exposed the superficial white matter. The procedure revealed distinguishable intergyral fibers, demonstrating their dissectability and enabling the identification of their orientation. The assessment of layer thickness was possible through direct observation and ex vivo morphological magnetic resonance imaging. Conclusion: The inside-out fiber technique effectively demonstrates intergyral association fibers in the post-mortem human brain. It adds to the neuroscience armamentarium, overcoming methodological obstacles and offering an anatomical substrate essential for neural circuit modeling and the evaluation of neuroimaging congruence. Impact statement The inside-out fiber dissection technique enables a totally new perception of cerebral connectivity as the observer navigates inside the parenchyma and looks toward the cerebral surface with the subcortical white matter and the cortical mantle in place. This approach has proven very effective for exposing intergyral association fibers, which have shown to be much more distinguishable from an inner perspective. It gave rise to unprecedented images of the human superficial white matter and allowed, for the first time, direct observation of this vast mantle of fascicles on entire cerebral hemisphere aspects.

Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks.

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce. Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12). We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold's bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl's gyrus. Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.

Neural correlates of mindfulness meditation and hypnosis on magnetic resonance imaging: similarities and differences. A scoping review.

BACKGROUND: Mindfulness meditation (MM) and hypnosis practices are gaining interest in mental health, but their physiological mechanisms remain poorly understood. This study aimed to synthesize the functional, morphometric and metabolic changes associated with each practice using magnetic resonance imaging (MRI), and to identify their similarities and differences. METHODS: MRI studies investigating MM and hypnosis in mental health, specifically stress, anxiety, and depression, were systematically screened following PRISMA guidelines from four research databases (PubMed, Web of Science, Embase, PsycINFO) between 2010 and 2022. RESULTS: In total, 97 references met the inclusion criteria (84 for MM and 13 for hypnosis). This review showed common and divergent points regarding the regions involved and associated brain connectivity during MM practice and hypnosis. The primary commonality between mindfulness and hypnosis was decreased default mode network intrinsic activity and increased central executive network - salience network connectivity. Increased connectivity between the default mode network and the salience network was observed in meditative practice and mindfulness predisposition, but not in hypnosis. CONCLUSIONS: While MRI studies provide a better understanding of the neural basis of hypnosis and meditation, this review underscores the need for more rigorous studies.

Right hemisphere and metaphor comprehension: A connectionist perspective.

Metaphor comprehension is a cognitively complex task, with evidence pointing to the engagement of multiple cerebral areas. In addition, the involvement of the right hemisphere appears to vary with cognitive effort. Therefore, the interconnecting pathways of such distributed cortical centers should be taken into account when studying this topic. Despite this, the potential contribution of white matter fasciculi has received very little attention in the literature to date and is not mentioned in most metaphor comprehension studies. To highlight the probable implications of the right inferior fronto-occipital fasciculus, right superior longitudinal system, and callosal radiations, we bring together findings from different research fields. The aim is to describe important insights enabled by the cross-fertilization of functional neuroimaging, clinical findings, and structural connectivity.

Using ex vivo arterial injection and dissection to assess white matter vascularization.

Advances in the techniques for assessing human cerebral white matter have recently contributed to greater attention to structural connectivity. Yet, little is known about the vascularization of most white matter fasciculi and the fascicular composition of the vascular territories. This paper presents an original method to label the arterial supply of macroscopic white matter fasciculi based on a standardized protocol for post-mortem injection of colored material into main cerebral arteries combined with a novel fiber dissection technique. Twelve whole human cerebral hemispheres obtained post-mortem were included. A detailed description of every step, from obtaining the specimen to image acquisition of its dissection, is provided. Injection and dissection were reproducible and manageable without any sophisticated equipment. They successfully showed the arterial supply of the dissected fasciculi. In addition, we discuss the challenges we faced and overcame during the development of the presented method, highlight its originality. Henceforth, this innovative method serves as a tool to provide a precise anatomical description of the vascularization of the main white matter tracts.

Anatomical study of the carotid-trigeminal interface: The missing link in the trigeminovascular system?

The trigeminal system is considered a prominent actor in brain nociceptive innervation. The trigeminovascular system is mainly composed of pseudounipolar neurons located within the trigeminal ganglion, whose dendrites originate in cerebral blood vessels. Anatomical studies demonstrating anatomical continuity between perivascular fibers and the trigeminal system are lacking. This issue is addressed in this study. Eleven cadaveric heads obtained from a body donation program were fixed in formalin. We performed a microanatomical study of the cavernous carotid-trigeminal interface and a histological examination of the tissue bridges crossing the virtual space between the medial aspect of the trigeminal ganglion and ophthalmic nerve and the lateral aspect of the cavernous segment of the internal carotid artery. Very strong adhesion was observed between the horizontal segment of the artery and the ophthalmic nerve in all specimens. The virtual space in this interface was crossed by a web of delicate filaments. Histological examination demonstrated the presence of nerve fibers in all samples. In this study, the carotid-trigeminal interface has been described in greater detail than ever before and could provide insight into disorders related to the trigeminovascular system. As the present results do not allow the exact nature of the axons to be affirmed, further investigation is necessary.

Cerebral white matter vasculature: still uncharted?

White matter vasculature plays a major role in the pathophysiology of permanent neurological deficits following a stroke or progressive cognitive alteration related to small vessel disease. Thus, knowledge of the complex vascularization and functional aspects of the deep white matter territories is paramount to comprehend clinical manifestations of brain ischaemia. This review provides a structured presentation of the existing knowledge of the vascularization of the human cerebral white matter from seminal historical studies to the current literature. First, we revisit the highlights of prenatal development of the endoparenchymal telencephalic vascular system that are crucial for the understanding of vessel organization in the adult. Second, we reveal the tangled history of debates on the existence, clinical significance and physiological role of leptomeningeal anastomoses. Then, we present how conceptions on white matter vascularization transitioned from the mixed ventriculopetal/ventriculofugal theory, in which a low-flow area was interposed in between concurrent arterial flows, to the purely ventriculopetal theory. The latter model explains variable white matter sensitivity to ischaemia by various organizations of ventriculopetal vessel terminals having different origin/length properties and interconnection patterns. Next, arteries supplying primarily the white matter are described according to their length and overall structure. Furthermore, the known distribution territories, to date, are studied in relation to primary anatomical structures of the human cerebral white matter, emphasizing the sparsity of the 'ground truth' data available in the literature. Finally, the implications for both large vessel occlusion and chronic small vessel disease are discussed, as well as the insights from neuroimaging. All things considered, we identify the need for further research on deep white matter vascularization, especially regarding the arterial supply of white matter fibre tracts.

What's your name again? A review of the superior longitudinal and arcuate fasciculus evolving nomenclature.

Studies of the superior longitudinal fasciculus (SLF) have multiplied in recent decades owing to methodological advances, but the absence of a convention for nomenclature remains a source of confusion. Here, we have reviewed existing nomenclatures in the context of the research studies that generated them and we have identified their agreements and disagreements. A literature search was conducted using PubMed/MEDLINE, Web-of-Science, Embase, and a review of seminal publications, without restrictions regarding publication date. Our search revealed that diffusion imaging, autoradiography, and fiber dissection have been the main methods contributing to tract designation. The first two have been particularly influential in systematizing the horizontal elements distant from the lateral sulcus. Twelve approaches to naming were identified, eight of them differing considerably from each other. The terms SLF and arcuate fasciculus (AF) were often used as synonyms until the second half of the 20th century. During the last 15 years, this has ceased to be the case in a growing number of publications. The term AF has been used to refer to the assembly of three different segments, or exclusively to long frontotemporal fibers. Similarly, the term SLF has been employed to denote the whole superior longitudinal associative system, or only the horizontal frontoparietal parts. As only partial correspondence can be identified among the available nomenclatures, and in the absence of an official designation of all anatomical structures that can be encountered in clinical practice, a high level of vigilance regarding the effectiveness of every oral or written act of communication is mandatory.

Hemisphere stroke: impact on the semantic lexical aspects of language.

OBJECTIVE: To investigate if right hemisphere stroke is associated with decreased lexical-semantic ability. METHODS: We compared subjects with right hemisphere brain damage after stroke with healthy controls using the validated version of the Montreal Evaluation of Communication to assess lexical-semantic domains of language. RESULTS: Sixteen patients and thirty-two controls were included. The post-stroke group with right hemispheric brain lesions showed considerable limitations in metaphor interpretation, fluency, and semantic judgment. CONCLUSION: Individuals with right hemisphere damage after stroke may present with language changes in the lexical-semantic aspects.

Composition and organization of the sagittal stratum in the human brain: a fiber dissection study.

OBJECTIVE: The sagittal stratum is divided into two layers. In classic descriptions, the stratum sagittale internum corresponds to optic radiations (RADs), whereas the stratum sagittale externum corresponds to fibers of the inferior longitudinal fasciculus. Although advanced for the time it was proposed, this schematic organization seems simplistic considering the recent progress on the understanding of cerebral connectivity and needs to be updated. Therefore, the authors sought to investigate the composition of the sagittal stratum and to detail the anatomical relationships among the macroscopic fasciculi. METHODS: The authors performed a layer-by-layer fiber dissection from the superolateral aspect to the ventricular cavity in 20 cadaveric human hemispheres. RESULTS: Diverse bundles of white matter were observed to contribute to the sagittal stratum and their spatial arrangement was highly consistent from one individual to another. This was the case of the middle longitudinal fasciculus, the inferior fronto-occipital fasciculus, the RADs, and other posterior thalamic radiations directed to nonvisual areas of the cerebral cortex. In addition, small contributions to the sagittal stratum came from the anterior commissure anteriorly and the inferior longitudinal fasciculus inferiorly. CONCLUSIONS: A general model of sagittal stratum organization in layers is possible, but the composition of the external layer is much more complex than is mentioned in classic descriptions. A small contribution of the inferior longitudinal fasciculus is the main difference between the present results and the classic descriptions in which this bundle was considered to entirely correspond to the stratum sagittale externum. This subject has important implications both for fundamental research and neurosurgery, as well as for the development of surgical approaches for the cerebral parenchyma and ventricular system.

The human cingulum: From the limbic tract to the connectionist paradigm.

The cingulum is a core component of the limbic lobe and part of the circuit that was described by Papez where environmental experiences become endowed with emotional awareness. Recent techniques for the study of cerebral connectivity have updated this fasciculus' morphology and led to the acknowledgment that its involvement in superior functions goes far beyond emotion processing. Long and robust, the cingulum is a long association fasciculus with terminations in all cerebral lobes. These observations plead for a pivotal rethinking of its role in the human brain and lead to the conclusion that to merely consider it as the main fasciculus of the limbic system was actually a reductionism. This paper summarizes the key facts regarding why the cingulum is now perceived as a primary interconnecting apparatus in the medial aspect of the cerebral hemisphere.

A novel 3D nanofibre scaffold conserves the plasticity of glioblastoma stem cell invasion by regulating galectin-3 and integrin-ß1 expression.

Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown. In order to recapitulate the composition and the topographic properties of the cerebral ECM in the migration of GICs, we have set up a new aligned polyacrylonitrile (PAN)-derived nanofiber (NF) scaffold. This system is suitable for drug screening as well as discrimination of the migration potential of different glioblastoma stem cells. Functionalisation with LN increases the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of GBM in vivo, is the upregulation of galectin-3 and integrin-ß1 in Gli4 cells migrating on our NF scaffold. Downregulation of Calpain-2 in GICs migrating in vivo along the CC and in vitro on LN-coated NF underlines a difference in the turnover of focal adhesion (FA) molecules between single-cell and collective types of migration.

Combining Proprioceptive Neuromuscular Facilitation and Virtual Reality for Improving Sensorimotor Function in Stroke Survivors: A Randomized Clinical Trial.

AIM: To assess a program combining virtual reality (VR) games and proprioceptive neuromuscular facilitation (PNF) and to compare it with the standalone techniques in stroke survivors. METHODS: A randomized controlled clinical trial. A total of 48 participants were recruited in the outpatient clinic of a University Hospital in Salvador, Brazil. They were randomly assigned to 3 groups (n = 16 each): PNF, VR, and PNF/VR. Participants attended twice-weekly 50-minute sessions over a 2-month period. The PNF/VR group performed both PNF and VR exercises employing Nintendo Wii electronic games. Motor performance was assessed before and immediately after the treatment using the Fugl-Meyer Assessment scale. RESULTS: An improvement in the mean scores was observed after treatment independent of the allocation group with significant intragroup changes: 14.5, 10.5, and 10.4 for PNF, VR, and PNF/VR, respectively. Score changes were also observed in the analyses of specific sections as follows: (1) a significant improvement in the passive movement and pain score was observed in the PNF and PNF/VR groups; (2) the same was observed for the motor function of the upper limb in all groups, for the motor function of the lower limb in the VR group and for balance in the PNF and PNF/VR groups. CONCLUSIONS: The use of a program combining virtual rehabilitation and PNF presented results that were comparable with those obtained with the isolated techniques.