Anatomy of superior olivary complex and lateral lemniscus in Etruscan shrew.

Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus's central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew's auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.

Anatomical Study of the Supratentorial Extension for the Retrolabyrinthine Presigmoid Approaches.

BACKGROUND: Supratentorial craniotomy represents the upper part of the combined trans-tentorial or the supra-infratentorial presigmoid approach. In this study, we provide qualitative and quantitative analyses for the supratentorial extension of the presigmoid retrolabyrinthine suprameatal approach (PRSA). METHODS: The infratentorial PRSA followed by the supratentorial extension craniotomy with dividing and removal of the tentorial strip were performed on both sides of 5 injected human cadaver heads (n = 10 sides). Quantitative analysis was performed for the surface area gained (surgical accessibility) by adding the supratentorial craniotomy. Qualitative analysis was performed for the parts of the brainstem, cranial nerves, and vascular structures that became accessible by adding the supratentorial craniotomy. The anatomical obstacles encountered in the added operative corridor were analyzed. RESULTS: The supratentorial extension of PRSA provides an increase in surgical accessibility of 102.65% as compared to the PRSA standalone. The mean surface area of the exposed brainstem is 197.98 (standard deviation: 76.222) and 401.209 (standard deviation: 123.96) for the infratentorial and the combined supra-infratentorial presigmoid approach, respectively. Exposure for parts of III, IV, and V cranial nerves is added after the extension, and the surface area of the outer craniotomy defect has increased by 60.32%. Parts of the basilar, anterior inferior cerebellar, and superior cerebellar arteries are accessible after the supratentorial extension. CONCLUSIONS: The supratentorial extension of PRSA allows access to the supra-trigeminal area of the pons and the lower part of the midbrain. Considering this surgical accessibility and exposure significantly assists in planning such complex approaches while targeting central skull base lesions.

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Objective: To study the microanatomic structure of the subtemporal transtentorial approach to the lateral side of the brainstem, and to provide anatomical information that will assist clinicians to perform surgeries on the lateral, circumferential, and petroclival regions of the brainstem. Methods: Anatomical investigations were conducted on 8 cadaveric head specimens (16 sides) using the infratemporal transtentorial approach. The heads were tilted to one side, with the zygomatic arch at its highest point. Then, a horseshoe incision was made above the auricle. The incision extended from the midpoint of the zygomatic arch to one third of the mesolateral length of the transverse sinus, with the flap turned towards the temporal part. After removing the bone, the arachnoid and the soft meninges were carefully stripped under the microscope. The exposure range of the surgical approach was observed and the positional relationships of relevant nerves and blood vessels in the approach were clarified. Important structures were photographed and the relevant parameters were measured. Results: The upper edge of the zygomatic arch root could be used to accurately locate the base of the middle cranial fossa. The average distances of the star point to the apex of mastoid, the star point to the superior ridge of external auditory canal, the anterior angle of parietomastoid suture to the superior ridge of external auditory canal, and the anterior angle of parietomastoid suture to the star point of the 10 adult skull specimens were 47.23 mm, 45.27 mm, 26.16 mm, and 23.08 mm, respectively. The subtemporal approach could fully expose the area from as high as the posterior clinoid process to as low as the petrous ridge and the arcuate protuberance after cutting through the cerebellar tentorium. The approach makes it possible to handle lesions on the ventral or lateral sides of the middle clivus, the cistern ambiens, the midbrain, midbrain, and pons. In addition, the approach can significantly expand the exposure area of the upper part of the tentorium cerebelli through cheekbone excision and expand the exposure range of the lower part of the tentorium cerebelli through rock bone grinding technology. The total length of the trochlear nerve, distance of the trochlear nerve to the tentorial edge of cerebellum, length of its shape in the tentorial mezzanine, and its lower part of entering into the tentorium cerebelli to the petrosal ridge were (16.95±4.74) mm, (1.27±0.73) mm, (5.72±1.37) mm, and (4.51±0.39) mm, respectively. The cerebellar tentorium could be safely opened through the posterior clinoid process or arcuate protrusion for localization. The oculomotor nerve could serve as an anatomical landmark to locate the posterior cerebral artery and superior cerebellar artery. Conclusion: Through microanatomic investigation, the exposure range and intraoperative difficulties of the infratemporal transtentorial approach can be clarified, which facilitates clinicians to accurately and safely plan surgical methods and reduce surgical complications.

Axial Sections of Brainstem Safe Entry Zones and Clinical Importance of Intrinsic Structures: A Review.

Brainstem surgery is more difficult and riskier than surgeries in other parts of the brain due to the high density of critical tracts and cranial nerves nuclei in this region. For this reason, some safe entry zones into the brainstem have been described. The main purpose of this article is to bring on the agenda the significance of the intrinsic structures of the safe entry zones to the brainstem. Having detailed information about anatomic localization of these sensitive structures is important to predict and avoid possible surgical complications. In order to better understand this complex anatomy, we schematically drew the axial sections of the brainstem showing the intrinsic structures at the level of 9 safe entry zones that we used, taking into account basic neuroanatomy books and atlases. Some illustrations are also supported with intraoperative pictures to provide better surgical orientation. The second purpose is to remind surgeons of clinical syndromes that may occur in case of surgical injury to these delicate structures. Advanced techniques such as tractography, neuronavigation, and neuromonitorization should be used in brainstem surgery, but detailed neuroanatomic knowledge about safe entry zones and a meticulous surgery are more important. The axial brainstem sections we have drawn can help young neurosurgeons better understand this complex anatomy.

Aging pattern of the brainstem based on volumetric measurement and optimized surface shape analysis.

The brainstem, a small and crucial structure, is connected to the cerebrum, spinal cord, and cerebellum, playing a vital role in regulating autonomic functions, transmitting motor and sensory information, and modulating cognitive processes, emotions, and consciousness. While previous research has indicated that changes in brainstem anatomy can serve as a biomarker for aging and neurodegenerative diseases, the structural changes that occur in the brainstem during normal aging remain unclear. This study aimed to examine the age- and sex-related differences in the global and local structural measures of the brainstem in 187 healthy adults (ranging in age from 18 to 70 years) using structural magnetic resonance imaging. The findings showed a significant negative age effect on the volume of the two major components of the brainstem: the medulla oblongata and midbrain. The shape analysis revealed that atrophy primarily occurs in specific structures, such as the pyramid, cerebral peduncle, superior and inferior colliculi. Surface area and shape analysis showed a trend of flattening in the aging brainstem. There were no significant differences between the sexes or sex-by-age interactions in brainstem structural measures. These findings provide a systematic description of age associations with brainstem structures in healthy adults and may provide a reference for future research on brain aging and neurodegenerative diseases.

Brainstem anatomy with 7-T MRI: in vivo assessment and ex vivo comparison.

BACKGROUND: The brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy. METHODS: We acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature. RESULTS: This in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology. CONCLUSIONS: The use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders. RELEVANCE STATEMENT: In vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation. KEY POINTS: • The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T). • In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures. • Ex vivo imaging and histology confirmed all the structures identified in vivo. • χ and frequency imaging revealed more brainstem structures than magnitude imaging.

Revisiting a Telencephalic Extent of the Ascending Reticular Activating System.

Is the cerebrum involved in its own activation to states of attention or arousal? "Telencephalon" is a term borrowed from embryology to identify not only the cerebral hemispheres of the forebrain, but also the basal forebrain. We review a generally undercited literature that describes nucleus basalis of Meynert, located within the substantia innominata of the ventrobasal forebrain, as a telencephalic extension of the ascending reticular activating formation. Although that formation's precise anatomical definition and localization have proven elusive over more than 70 years, a careful reading of sources reveals that there are histological features common to certain brainstem neurons and those of the nucleus basalis, and that a largely common dendritic architecture may be a morphological aspect that helps to define non-telencephalic structures of the ascending reticular activating formation (e.g., in brainstem) as well as those parts of the formation that are telencephalic and themselves responsible for cortical activation. We draw attention to a pattern of dendritic arborization described as "isodendritic," a uniform (isos-) branching in which distal dendrite branches are significantly longer than proximal ones. Isodendritic neurons also differ from other morphological types based on their heterogeneous, rather than specific afferentation. References reviewed here are consistent in their descriptions of histology, particularly in studies of locales rich in cholinergic neurons. We discuss the therapeutic implications of a basal forebrain site that may activate cortex. Interventions that specifically target nucleus basalis and, especially, the survival of its constituent neurons may benefit afflictions in which higher cortical function is compromised due to disturbed arousal or attentiveness, including not only coma and related syndromes, but also conditions colloquially described as states of cognitive "fog" or of "long-haul" mental compromise.

A Novel Human Brainstem Map Based on True-Color Sectioned Images.

BACKGROUND: Existing atlases for the human brainstem were generated from magnetic resonance images or traditional histologically stained slides, but both are insufficient for the identification of detailed brainstem structures at uniform intervals. METHODS: A total of 319 sectioned images of the brainstem were selected from whole-body axial sectioned images, then coronal and sagittal sectioned images were reconstructed from the horizontal images. The fine and detailed structures were annotated in PowerPoint slides, then the volume model was produced and some white matter fibers were traced using MRIcroGL. RESULTS: In this study, a novel brainstem atlas based on sectioned images was generated that shows the true color and shape, as well as the accurate location of the nuclei and tracts; it reveals the striking contrast between gray and white matter, as well as fine structures. In total, 212 structures, including nuclei and tracts, were annotated in axial, coronal, and sagittal plane views of sectioned images (48-bit true color; 0.2 mm intervals, 0.06 mm × 0.06 mm pixel size). To verify the accuracy of the annotations, a volume model of the brainstem was constructed for independent observations of the three planes. CONCLUSION: In this paper, we describe several interesting structures included in the atlas. By depicting the fine structures of the human brainstem in detail, this atlas allows comprehensive understanding of the complicated topographies of the brainstem. As such, it will be of value for neuroanatomy education and research, in addition to enriching the literature on the human brain.

Microanatomy of the central myelin portion and transitional zone of the oculomotor and abducens nerves.

BACKGROUND: The microanatomy of the central myelin portion and transitional zone of several cranial nerves including trigeminal, facial, vestibulocochlear, glossopharyngeal, and vagus nerves have been clearly demonstrated to provide information for neurovascular compression syndrome such as trigeminal neuralgia and hemifacial spasm. However, the study of oculomotor and abducens nerve is limited. MATERIALS AND METHODS: Oculomotor and abducens nerves were harvested with a portion of brainstem and embedded in paraffin. Longitudinal and serial sections from ten of each cranial nerve were stained and a photomicrograph was taken to make the following observations and measurements: 1) patterns of central myelin portion, 2) length of central myelin portion, and 3) depth of central myelin- peripheral myelin transitional zone. RESULTS: For oculomotor nerve, the longest central myelin bundle was always seen on the first nerve bundle and that the length of central myelin decreased gradually. For abducens nerve, morphological patterns were classified into four types based on number of nerve rootlets emerging from the brainstem and number of nerve bundles in each rootlet. Length of central myelin portion was between 0.36-6.10 mm (2.75 ± 0.83 mm) and 0.13-5.01 mm (1.66 ± 1.39 mm) for oculomotor and abducens nerves, respectively. The oculomotor nerve transitional zone depth was 0.07-058 mm (0.23 ± 0.07 mm), while for abducens nerve, depth was 0.05-0.40 mm (0.16 ± 0.07 mm). Positive weak correlations between central myelin and depth of TZ were found in oculomotor nerve (r +0.310, p < 0.05) and abducens nerves (r +0.413, p < 0.05). CONCLUSIONS: Detailed microanatomy of the central myelin and transitional zone might be beneficial for locating the site of compression in neurovascular conflicts at oculomotor and abducens nerves.

A brainstem map for visceral sensations.

The nervous system uses various coding strategies to process sensory inputs. For example, the olfactory system uses large receptor repertoires and is wired to recognize diverse odours, whereas the visual system provides high acuity of object position, form and movement1-5. Compared to external sensory systems, principles that underlie sensory processing by the interoceptive nervous system remain poorly defined. Here we developed a two-photon calcium imaging preparation to understand internal organ representations in the nucleus of the solitary tract (NTS), a sensory gateway in the brainstem that receives vagal and other inputs from the body. Focusing on gut and upper airway stimuli, we observed that individual NTS neurons are tuned to detect signals from particular organs and are topographically organized on the basis of body position. Moreover, some mechanosensory and chemosensory inputs from the same organ converge centrally. Sensory inputs engage specific NTS domains with defined locations, each containing heterogeneous cell types. Spatial representations of different organs are further sharpened in the NTS beyond what is achieved by vagal axon sorting alone, as blockade of brainstem inhibition broadens neural tuning and disorganizes visceral representations. These findings reveal basic organizational features used by the brain to process interoceptive inputs.

Auditory brainstem development of naked mole-rats (Heterocephalus glaber).

Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel Kv3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and Kv3.3 protein levels in the brainstem.

Nuclear organization of serotonergic neurons in the brainstems of a lar gibbon and a chimpanzee.

In the current study, we detail, through the analysis of immunohistochemically stained sections, the morphology and nuclear parcellation of the serotonergic neurons present in the brainstem of a lar gibbon and a chimpanzee. In general, the neuronal morphology and nuclear organization of the serotonergic system in the brains of these two species of apes follow that observed in a range of Eutherian mammals and are specifically very similar to that observed in other species of primates. In both of the apes studied, the serotonergic nuclei could be readily divided into two distinct groups, a rostral and a caudal cluster, which are found from the level of the decussation of the superior cerebellar peduncle to the spinomedullary junction. The rostral cluster is comprised of the caudal linear, supralemniscal, and median raphe nuclei, as well as the six divisions of the dorsal raphe nuclear complex. The caudal cluster contains several distinct nuclei and nuclear subdivisions, including the raphe magnus nucleus and associated rostral and caudal ventrolateral (CVL) serotonergic groups, the raphe pallidus, and raphe obscurus nuclei. The one deviation in organization observed in comparison to other primate species is an expansion of both the number and distribution of neurons belonging to the lateral division of the dorsal raphe nucleus in the chimpanzee. It is unclear whether this expansion occurs in humans, thus at present, this expansion sets the chimpanzee apart from other primates studied to date.

Microsurgical anatomy of safe entry zones on the ventrolateral brainstem: a morphometric study.

Surgery of the brainstem is challenging due to the complexity of the area with cranial nerve nuclei, reticular formation, and ascending and descending fibers. Safe entry zones are required to reach the intrinsic lesions of the brainstem. The aim of this study was to provide detailed measurements for anatomical landmark zones of the ventrolateral surface of the human brainstem related to previously described safe entry zones. In this study, 53 complete and 34 midsagittal brainstems were measured using a stainless caliper with an accuracy of 0.01 mm. The distance between the pontomesencephalic and bulbopontine sulci was measured as 26.94 mm. Basilar sulcus-lateral side of pons (origin of the fibers of the trigeminal nerve) distance was 17.23 mm, transverse length of the pyramid 5.42 mm, and vertical length of the pyramid 21.36 mm. Lateral mesencephalic sulcus was 12.73 mm, distance of the lateral mesencephalic sulcus to the oculomotor nerve 13.85 mm, and distance of trigeminal nerve to the upper tip of pyramid 17.58 mm. The transverse length for the inferior olive at midpoint and vertical length were measured as 5.21 mm and 14.77 mm, consequently. The thickness of the superior colliculus was 4.36 mm, and the inferior colliculus 5.06 mm; length of the tectum was 14.5 mm and interpeduncular fossa 11.26 mm. Profound anatomical knowledge and careful analysis of preoperative imaging are mandatory before surgery of the brainstem lesions. The results presented in this study will serve neurosurgeons operating in the brainstem region.

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology.

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template "SC21" from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

A high-resolution interactive atlas of the human brainstem using magnetic resonance imaging.

Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in liquid fluorocarbon. MRI was performed in a 7-Tesla scanner with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 h and 208 h, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy. Anatomic and diffusion images were rendered with isotropic resolutions of 50 µm and 200 µm, respectively. Ninety different structures were segmented and labeled, and 11 different fiber bundles were rendered with tractography. The complete atlas is available online for interactive use at https://www.civmvoxport.vm.duke.edu/voxbase/login.php?return_url=%2Fvoxbase%2F. This atlas presents multiple contrasting datasets and selected tract reconstruction with unprecedented resolution for MR imaging of the human brainstem. There are immediate applications in neuroanatomical education, with the potential to serve future applications for neuroanatomical research and enhanced neurosurgical planning through "safe" zones of entry into the human brainstem.

WIKIBrainStem: An online atlas to manually segment the human brainstem at the mesoscopic scale from ultrahigh field MRI.

The brainstem is one of the most densely packed areas of the central nervous system in terms of gray, but also white, matter structures and, therefore, is a highly functional hub. It has mainly been studied by the means of histological techniques, which requires several hundreds of slices with a loss of the 3D coherence of the whole specimen. Access to the inner structure of the brainstem is possible using Magnetic Resonance Imaging (MRI), but this method has a limited spatial resolution and contrast in vivo. Here, we scanned an ex vivo specimen using an ultra-high field (11.7T) preclinical MRI scanner providing data at a mesoscopic scale for anatomical T2-weighted (100 µm and 185 µm isotropic) and diffusion-weighted imaging (300 µm isotropic). We then proposed a hierarchical segmentation of the inner gray matter of the brainstem and defined a set of rules for each segmented anatomical class. These rules were gathered in a freely accessible web-based application, WIKIBrainStem (https://fibratlas.univ-tours.fr/brainstems/index.html), for 99 structures, from which 13 were subdivided into 29 substructures. This segmentation is, to date, the most detailed one developed from ex vivo MRI of the brainstem. This should be regarded as a tool that will be complemented by future results of alternative methods, such as Optical Coherence Tomography, Polarized Light Imaging or histology… This is a mandatory step prior to segmenting multiple specimens, which will be used to create a probabilistic automated segmentation method of ex vivo, but also in vivo, brainstem and may be used for targeting anatomical structures of interest in managing some degenerative or psychiatric disorders.

Genetic scores for adult subcortical volumes associate with subcortical volumes during infancy and childhood.

Individual differences in subcortical brain volumes are highly heritable. Previous studies have identified genetic variants that underlie variation in subcortical volumes in adults. We tested whether those previously identified variants also affect subcortical regions during infancy and early childhood. The study was performed within the Generation R study, a prospective birth cohort. We calculated polygenic scores based on reported GWAS for volumes of the accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus. Participants underwent cranial ultrasound around 7 weeks of age (range: 3-20), and we obtained metrics for the gangliothalamic ovoid, a predecessor of the basal ganglia. Furthermore, the children participated in a magnetic resonance imaging (MRI) study around the age of 10 years (range: 9-12). A total of 340 children had complete data at both examinations. Polygenic scores primarily associated with their corresponding volumes at 10 years of age. The scores also moderately related to the diameter of the gangliothalamic ovoid on cranial ultrasound. Mediation analysis showed that the genetic influence on subcortical volumes at 10 years was only mediated for 16.5-17.6% of the total effect through the gangliothalamic ovoid diameter at 7 weeks of age. Combined, these findings suggest that previously identified genetic variants in adults are relevant for subcortical volumes during early life, and that they affect both prenatal and postnatal development of the subcortical regions.

Neuroanatomical MRI study: reference values for the measurements of brainstem, cerebellar vermis, and peduncles.

OBJECTIVES: To set age-specific normal reference values for brainstem, cerebellar vermis, and peduncles measurements and characterize values' variations according to gender, age, and age by gender interaction. METHODS: 565 normal brain magnetic resonance examinations with normal anatomy and signal intensity of the supra- and infratentorial structures were categorized into six age groups (infant, child, adolescent, young adult, middle-age adult, and old aged adults). Patients with congenital malformations, gross pathology of the supra- or infratentorial brain, brain volume loss, developmental delay, metabolic disorders, and neuropsychological disorders (n = 2.839) were excluded. On midsagittal T1 weighted and axial T2 weighted images specific linear diameters and ratios of the brainstem, cerebellar vermis, and peduncles were attained. Two observers assessed a random sample of 100 subjects to evaluate the inter- and intraobserver reproducibility. Intraclass correlation coefficients, means ± standard deviation, one and two-way analysis of variance tests were used in the statistical analysis. RESULTS: Good to excellent inter- and intraobserver measurements' reproducibility were observed, except for the transverse diameter of the midbrain, the anteroposterior diameter of the medulla oblongata at the pontomedullary and cervicomedullary junctions, cerebellar vermis anteroposterior diameter, and thickness of the superior cerebellar peduncle. Age-specific mean values of the investigated measurements were established. A significant gender-related variation was recorded in the anteroposterior diameter of the basis pontis (p = 0.044), the anteroposterior diameter of the medulla oblongata at the cervicomedullary junction (p = 0.044), and cerebellar vermis height (p = 0.018). A significant age-related change was detected in all measurements except the tectal ratio. Age by gender interaction had a statistically significant effect on the tectal ratio, inferior, and middle cerebellar peduncles' thickness (p = 0.001, 0.022, and 0.028, respectively). CONCLUSION: This study provides age-specific normal mean values for various linear dimensions and ratios of the posterior fossa structures with documentation of measurements' variability according to gender, age, and their interaction. ADVANCES IN KNOWLEDGE: It provides a valuable reference in the clinical practice for easier differentiation between physiological and pathological conditions of the posterior fossa structures especially various neurodegenerative diseases and congenital anomalies.

Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature.

OBJECTIVE: The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. METHODS: The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. RESULTS: The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. CONCLUSIONS: The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.

Microsurgical anatomy of the fourth ventricle.

Anatomical description of the fourth ventricle is essential for an accurate understanding of its related tumoral pathologies and surgical approach respecting cerebellar and brainstem structures. Numerous cadaver pictures illustrate this chapter which contains V4 floor and roof description and its vascularization.