Mapping the rest of the human connectome: Atlasing the spinal cord and peripheral nervous system.

The emergence of diffusion, structural, and functional neuroimaging methods has enabled major multi-site efforts to map the human connectome, which has heretofore been defined as containing all neural connections in the central nervous system (CNS). However, these efforts are not structured to examine the richness and complexity of the peripheral nervous system (PNS), which arguably forms the (neglected) rest of the connectome. Despite increasing interest in an atlas of the spinal cord (SC) and PNS which is simultaneously stereotactic, interactive, electronically dissectible, scalable, population-based and deformable, little attention has thus far been devoted to this task of critical importance. Nevertheless, the atlasing of these complete neural structures is essential for neurosurgical planning, neurological localization, and for mapping those components of the human connectome located outside of the CNS. Here we recommend a modification to the definition of the human connectome to include the SC and PNS, and argue for the creation of an inclusive atlas to complement current efforts to map the brain's human connectome, to enhance clinical education, and to assist progress in neuroscience research. In addition to providing a critical overview of existing neuroimaging techniques, image processing methodologies and algorithmic advances which can be combined for the creation of a full connectome atlas, we outline a blueprint for ultimately mapping the entire human nervous system and, thereby, for filling a critical gap in our scientific knowledge of neural connectivity.

When botany inspired pathology of the peripheral nervous system.

Medicine and botany are 2 distinct disciplines of "natural science," one focusing on humans, the other on plants. However, among the life sciences, both were quite close in earlier times. Moreover, the history of neuropathology, especially in the field of the peripheral nervous system, has been marked by many examples of "botanical images" used to describe certain histopathologic structures. We propose to better understand the reasons why neuropathologists used these botanical terms from a number of interesting anecdotes.

Sensory innervation of the human shoulder joint: the three bridges to break.

BACKGROUND: Painful shoulders create a substantial socioeconomic burden and significant diagnostic challenge for shoulder surgeons. Consensus with respect to the anatomic location of sensory nerve branches is lacking. The aim of this literature review was to establish consensus with respect to the anatomic features of the articular branches (ABs) (1) innervating the shoulder joint and (2) the distribution of sensory receptors about its capsule and bursae. MATERIALS AND METHODS: Four electronic databases were queried, between January 1945 and June 2019. Thirty original articles providing a detailed description of the distribution of sensory receptors about the shoulder joint capsule (13) and its ABs (22) were reviewed. RESULTS: The suprascapular, lateral pectoral, axillary, and lower subscapular nerves were found to provide ABs to the shoulder joint. The highest density of nociceptors was found in the subacromial bursa. The highest density of mechanoreceptors was identified within the insertion of the glenohumeral ligaments. The most frequently identified innervation pattern comprised 3 nerve bridges (consisting of ABs from suprascapular, axillary, and lateral pectoral nerves) connecting the trigger and the identified pain generator areas rich in nociceptors. CONCLUSION: Current literature supports the presence of a common sensory innervation pattern for the human shoulder joint. Anatomic studies have demonstrated that the most common parent nerves supplying ABs to the shoulder joint are the suprascapular, lateral pectoral, and axillary nerves. Further studies are needed to assess both the safety and efficacy of selective denervation of the painful shoulders, while limiting the loss of proprioceptive function.

Stereology of the Peripheral Nervous System.

Qualitative histopathology has been the gold standard for evaluation of morphological tissue changes in all organ systems, including the peripheral nervous system. However, the human eye is not sensitive enough to detect small changes in quantity or size. Peripheral nervous system toxicity can manifest as subtle changes in neuron size, neuron number, axon size, number of myelinated or unmyelinated axons, or number of nerve fibers. Detection of these changes may be beyond the sensitivity of the human eye alone, necessitating quantitative approaches in some cases. Although 2-dimensional (2D) histomorphometry can provide additional information and is more sensitive than qualitative evaluation alone, the results are not always representative of the entire tissue and assumptions about the tissue can lead to bias, or inaccuracies, in the data. Design-based stereology provides 3D estimates of number, volume, surface area, or length, and stereological principles can be applied to peripheral nervous system tissues to obtain accurate and precise estimates, such as neuron number and size, axon number, and total intraepidermal nerve fiber length. This review describes practical stereological approaches to 3 compartments of the peripheral nervous system: ganglia, peripheral nerves, and intraepidermal nerve fibers.

Nerve Surgeons' Assessment of the Role of Eduard Pernkopf's Atlas of Topographic and Applied Human Anatomy in Surgical Practice.

BACKGROUND: Pernkopf's atlas of Anatomy contains anatomical plates with detailed images of the peripheral nerves. Its use is controversial due to the author's association with the "Third Reich" and the potential depiction of victims of the Holocaust. The ethical implications of using this atlas for informing surgical planning have not been assessed. OBJECTIVE: To (1) assess the role of Pernkopf's atlas in nerve surgeons' current practice and (2) determine whether a proposal for its ethical handling may provide possible guidance for use in surgery and surgical education. METHODS: Members of American Society for Peripheral Nerve and PASSIO Education (video-based learning platform) were surveyed and 182 responses collected. The survey introduced the historical origin of Pernkopf's atlas, and respondents were asked whether they would use the atlas under specific conditions to serve as a recommendation for its ethical handling. An anatomical plate comparison between Netter's and Pernkopf's atlases was performed to compare anatomical accuracy and surgical utility. RESULTS: Fifty-nine percent of respondents were aware of Pernkopf's atlas, with 13% currently using it. Aware of the historical facts, 69% were comfortable using the atlas, 15% uncomfortable, and 17% undecided. Additional information on conditions for an ethical approach to the use of the atlas led 76% of those "uncomfortable" and "undecided" to becoming "comfortable" with use. CONCLUSION: While the use of Pernkopf's atlas remains controversial, a proposal detailing conditions for an ethical approach in its use provides new guidance in surgical planning and education.

Revisiting Avicenna's (ad 980-1037) Anatomical Concepts of the Musculoskeletal and Peripheral Nervous Systems in the Canon of Medicine

Avicenna, as he is known in the West, was a famous Persian Muslim physician and influential philosopher-scientist of the medieval Islamic world. He wrote and compiled the Canon of Medicine text, a book which was adopted as the main text of medicine at the most Persian and Western universities. The book consists of basic medical sciences, applied clinical sciences and pharmacology. In the current study, we present an analysis of the anatomy of the musculoskeletal and peripheral nervous systems as viewed by Avicenna in the Canon of Medicine, and compare them with the relevant modern literature.

Clinical anatomy of fecal incontinence in women.

Fecal incontinence is a devastating condition that has a severe impact on quality of life. This condition disproportionately affects women and its incidence is increasing with the aging United States population. Fecal continence is maintained by coordination of a functioning anal sphincter complex, intact sensation of the anorectum, rectal compliance, and the ability to consciously control defecation. Particularly important are the puborectalis sling of the levator ani muscle complex and intact innervation of the central and peripheral nervous systems. An understanding of the intricate anatomy required to maintain continence and regulate defecation will help clinicians to provide appropriate medical and surgical management and diminish the negative impact of fecal incontinence. In this article, we describe the anatomic and neural basis of fecal continence and normal defecation as well as changes that occur with fecal incontinence in women. Clin. Anat. 30:901-911, 2017. © 2017 Wiley Periodicals, Inc.

Descrição anatômica do plexo braquial de Callithrix jacchus e Callithrix penicillata / Anatomic description of brachial plexus of Callithrix jacchus and Callithrix penicillata

Callithrix jacchus e Callithrix penicillata são primatas de pequeno porte cuja utilização como modelo anatômico tem se mostrado cada vez mais frequente, não somente pela praticidade no manuseio como facilidade no trato em criatório e sua taxa de reprodução. Este estudo teve como objetivo descrever os componentes dos plexos braquial em Callithrix jacchus e penicillata. Para tanto, três espécimes com aproximadamente 8 anos e 240 g foram fixados em solução de formaldeído a 10%, e posteriormente dissecados e fotodocumentados. O plexo braquial do Callithrix jacchus e penicillata originou-se dos nervos espinhais C5 a T1 constituindo os troncos cranial, médio e caudal. A composição do plexo braquial destes animais se assemelha ao de outros primatas, bem como a outros mamíferos.(AU)

Callithrix jacchus and Callithrix penicillata are small primates used as anatomic model, not only for convenience in handling as ease in regard to breeding and reproductive rate. The aim of this study was to describe the components of the brachial plexus in Callithrix jacchus and C. penicillata. Three specimens about 8 years old and weighing 240g were fixed in 10% formaldehyde and subsequently dissected and photodocumented. The brachial plexus of Callithrix jacchus and C. penicillata originates from the spinal nerves C5 to T1 in continuation of the cranial, medium and flow trunk. The composition of the brachial plexus of these animals is similar to the one of other primates ands other mammals.(AU)

From mouth to anus: Functional and structural relevance of enteric neurons in the Drosophila melanogaster gut.

The intestinal tract is the main organ involved in host nutritional homeostasis. Intestinal function in both vertebrates and invertebrates is partly controlled by enteric neurons that innervate the gut. Though anatomical and functional aspects of enteric neurons are relatively less characterized in Drosophila than in large insects, analyses of the role of the enteric neurons in flies have remarkably progressed in the last few years. In this review, we first provide a summary of the structure and function of the Drosophila intestine. We then discuss recent studies of the structure and function of enteric neurons in Drosophila melanogaster.

Andreas Vesalius as a renaissance innovative neuroanatomist: his 5th centenary of birth.

Andreas Vesalius (1514-1564) is considered the Father of Modern Anatomy, and an authentic representative of the Renaissance. His studies, founded on dissection of human bodies, differed from Galeno, who based his work on dissection of animals, constituted a notable scientific advance. Putting together science and art, Vesalius associated himself to artists of the Renaissance, and valued the images of the human body in his superb work De Humani Corporis Fabrica.This paper aims to honor this extraordinary European Renaissance physician and anatomist, who used aesthetic appeal to bind text and illustration, science and art. His achievements are highlighted, with an especial attention on neuroanatomy. Aspects about his personal life and career are also focused.

Neural control of the lower urinary tract.

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

Peripheral nerve segmentation using Nonparametric Bayesian Hierarchical Clustering.

Several cases related to chronic pain, due to accidents, illness or surgical interventions, depend on anesthesiology procedures. These procedures are assisted with ultrasound images. Although, the ultrasound images are a useful instrument in order to guide the specialist in anesthesiology, the lack of intelligibility due to speckle noise, makes the clinical intervention a difficult task. In a similar manner, some artifacts are introduced in the image capturing process, challenging the expertise of anesthesiologists for not confusing the true nerve structures. Accordingly, an assistance methodology using image processing can improve the accuracy in the anesthesia practice. This paper proposes a peripheral nerve segmentation method in medical ultrasound images, based on Nonparametric Bayesian Hierarchical Clustering. The experimental results show segmentation performances with a Mean Squared Error performance of 1.026 ± 0.379 pixels for ulnar nerve, 0.704 ± 0.233 pixels for median nerve and 1.698 ± 0.564 pixels for peroneal nerve. Likewise, the model allows to emphasize other soft structures like muscles and aqueous tissues, that might be useful for an anesthesiologist.

Neurografía por resonancia magnética en la evaluación de los nervios periféricos / Magnetic resonance neurography in the evaluation of peripheral nerves

Magnetic resonance neurography (MRN), with high resolution sequences, allows for a detailed study of the plexus and peripheral nerves. For its interpretation, it is necessary to have a general knowledge of MR, as well as of the anatomy of the neuromuscular system and lesions that affect it. Nerve and plexus pathology can be divided into mononeuropathies (for trauma, entrapment or tumors) and hereditary polyneuropathies (such as Charcot-Marie-Tooth disease) or acquired (for chronic idiopathic demyelinating polyradiculoneuropathy, diabetes, vasculitis or inflammation). The objective of this review is to describe the study technique of Magnetic Resonance Neurography as well as the characteristics of the normal and pathological peripheral nerve.

La neurografía por resonancia magnética (NRM), con secuencias de alta resolución, permite un detallado estudio de los plexos y nervios periféricos. Para su interpretación, es necesario contar con conocimientos generales de RM, así como de la anatomía del sistema neuromuscular y de las lesiones que lo afectan. La patología de los nervios y plexos puede dividirse en mononeuropatías (por trauma, atrapamiento o tumores) y polineuropatías hereditarias (como la enfermedad de Charcot Marie Tooth) o adquiridas (por poliradiculoneuropatía desmielinizante idiopática crónica, diabetes, vasculitis o inflamación) El objetivo de esta revisión es describir la técnica de estudio de la neurografía por resonancia magnética, así como las características del nervio periférico normal y patológico.

[New insights on the organization of the nodes of Ranvier]. / Nouveautés sur les mécanismes de formation des nœuds de Ranvier.

Myelin plays a crucial role in the rapid and saltatory conduction of the nerve impulse along myelinated axons. In addition, myelin closely regulates the organization of the axonal compartments. This organization involves several complex mechanisms including axo-glial contact, diffusion barriers, the cytoskeletal network, and the extracellular matrix. In peripheral nerves, the axo-glial contact dictates the formation of the nodes and the clustering of the voltage-gated sodium channels (Nav). The axo-glial contact at nodes implicates adhesion molecules expressed by the Schwann cell (gliomedin and NrCAM), which binds a partner, neurofascin-186, on the axonal side. This complex is essential for the recruitment of ankyrin-G, a cytoskeletal scaffolding protein, which binds and concentrates Nav channels at nodes. The paranodal junctions flanking the nodes also play a complementary function in node formation. These junctions are formed by the association of contactin-1/caspr-1/neurofascin-155 and create a diffusion barrier, which traps proteins at the nodes and dampens their diffusion along the internode. In the central nervous system, the mechanisms of node formation are different and the formation of the paranodal junctions precedes the aggregation of Nav channels at nodes. However, node formation can still happen in absence of paranodal junctions in the CNS. One explanation is that NF186 interacts with components of the extracellular matrix around the node and thereby stabilizes the aggregation of nodal proteins. It is likely that many other proteins are also implicated in the signaling pathways that regulate the differentiation of the axonal compartments. The nature and function of these proteins are yet to be identified.

Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

Experience with examination of the spinal cord and peripheral nervous system (PNS) in mice: A brief overview.

The representative areas for examination of the mouse peripheral nervous system are the spinal cord, containing central components of the peripheral nervous system that needs to be examined at least at cervical and lumbar level, the sciatic and the tibial nerve. Skeletal muscle samples should include the soleus muscle and the quadriceps femoris or long digital extensor, as well as the medial gastrocnemius. Examination can be extended to the thoracic spinal cord, lumbar dorsal root ganglia and spinal nerve roots, as well as the plantar nerve, and other areas of interest. Perfusion fixation is considered optimal for the nervous system; however, immersion fixation allows producing microscopic sections of excellent quality as well. Paraffin-embedded, hematoxylin and eosin-stained sections can be made from all areas, save for small nerves such as the tibial or plantar nerve, which are examined with advantage in hard plastic sections. It is possible to produce hard plastic sections also of the vertebral column, including the spinal cord, dorsal root ganglia and nerve roots. For special investigations, mice can be fixed in toto, decalcified, embedded and sectioned to reveal the areas of interest. In the mouse peripheral nerves, myelination progresses until the adult age. In aging peripheral nerves there is axonal atrophy, degeneration, nerve fiber loss, increase of collagen and sporadic demyelination, especially radiculoneuropathy. The dorsal root ganglia of untreated control animals show frequent cytoplasmic vacuolation. Axonal degeneration is distally, primary demyelination proximally accentuated. Mouse is not very sensitive to peripheral neurotoxicity: to induce toxic peripheral neuropathy mostly parenteral administration and/or newborn animals are used. Naturally occurring infection affecting the spinal cord and peripheral nerves is Theiler's encephalomyelitis virus inducing acute poliomyelitis or chronic demyelination. Any experimental results are to be assessed taking into account spontaneous, age-related, background changes.

Intraoperative mapping of roots, plexuses, and nerves.

The use of intraoperative mapping of neural structures has come to be an indispensable technique to prevent or minimize postoperative morbidity. In this article, I briefly mention its use in mapping nerve roots, plexuses, and peripheral nerves. The reader may find some mention of monitoring techniques, too, as monitoring and mapping are seldom done separately. I include the technical details of different mapping modalities, relevant anatomy, and clinical applications, as appropriate.

Gross anatomy and development of the peripheral nervous system.

The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS.

Innervation and histology of the clitoral-urethal complex: a cross-sectional cadaver study.

INTRODUCTION: Despite its central role in sexual function, we lack a description of the nerve distribution and histology for the central components of the clitoris. AIM: This study aims to characterize microscopic anatomy of the clitoral-urethral complex (CUC) and aid our understanding of sexual sensation METHODS: The CUC was excised from three female fresh-frozen cadavers en bloc and prepared in 5-µm longitudinal sections with hematoxylin and eosin and S100 immunohistochemistry for neural elements. Approximately 20 sections were obtained from each specimen. On low power microscopy, the 30 most innervated fields on each section were identified. On high power, the total number of nerves per field was quantified, then was averaged. The histologic characteristics of each clitoral component were described. Two investigators evaluated all specimens. MAIN OUTCOME MEASURES: Descriptives of large (≥3 fibers) and small nerves based on location in the CUC. RESULTS: Nerve quantification revealed the glans to be the most populated by small nerves (52.1, standard deviation [SD] 26.2). As slices through each specimen moved caudad toward the urethra, the number of small nerves dramatically decreased from 40.4 (SD 10.8) in the body and 29.8 (SD 8.8) (superior CUC) near the bulb to 23.7 (SD 9.8) in the middle CUC and 20.5 (SD 10.4) (inferior CUC) near the urethra. Although the variation in small nerves was striking, large nerves were somewhat uniform and comprised a minority of the overall quantity. Neuroanatomy was consistent for all cadaver specimens. CONCLUSIONS: Our study provided a description of the nerve distribution throughout the central CUC. Increased density of small nerves in the glans suggests this is the location of heightened sensation. Decreasing quantity of nerves in segments closer to the urethra may indicate these zones are less important for sexual sensation. Knowledge of human clitoral innervation is important for understanding the complexities of the female sexual response cycle.