MEID 608

NEUROSCIENCE LABORATORY SYLLABUS

BY

JOHN B. GELDERD, Ph.D.

The illustrations within the text of this laboratory syllabus were created by Joan Quarles. Selected illustrations within the syllabus were modified from published illustrations by Frank Netter, MD with the permission of Novartis Medical Education, Whippany, NJ. TABLE OF CONTENTS

Lab Date Laboratory Session Pages Exam 1 1 January 3rd Gross Anatomy of the Brain 6 – 13 Meninges 14 – 16 2 January 4th Blood Supply 17 – 22 CSF and Ventricles of the Brain 23 – 26 Introduction to the Macroscopic Anatomy of the 3 January 7th 27 – 32 Neuraxis Ascending Sensory Pathways 33 – 36 4 January 8th Sensory Pathways for the Anterior 2/3 of the Head 37 – 39 Exam 2 5 January 14th Pyramidal System 40 – 43 Cranial Nerves 44 – 52 6 January 16th Neuroround 53 Basal Ganglia 54 – 58 7 January 17th Neuroround 59 Cerebellum 60 – 67 8 January 18th Neuroround 68 Exam 3 Vestibular System 69 – 70 9 January 30th Auditory System 71 – 73 10 January 31st Visual System 74 – 77 Diencephalon (Hypothalamus) 78 – 81 11 February 1st Limbic System 82 – 87 Cortex and Review 88 – 93 12 February 4th Neuroround 1 – 2 94 – 97 Labeled Slides from Slide Set 98 – 116

Neuroscience Laboratory Manual 2 INTRODUCTION

The purpose of this syllabus is to assist and guide the student through the neuroscience laboratory portion of Neuroscience (MEID 608) in a systematic fashion. It has been prepared specifically for the curriculum at the Texas A&M University College of Medicine. The ultimate goal of the laboratory portion of this course is to provide a "hands on" experience in learning and understanding the FUNCTIONAL anatomy of the human central nervous system (CNS). To assist you in this endeavor, this syllabus will be used in conjunction with the following laboratory materials:

1. The Medical Neuroscience Laboratory Manual (downloaded from eCampus under MEID608 Neuroscience). This file contains the Neuroscience Manual & Slide Set.

2. Two Brain Buckets (shared by a MDL group) containing: #: Whole and Half Brain #A: Horizontally and Coronally Sectioned Brains

3. An Atlas of Neuroanatomy. Each laboratory group will receive one copy of the “Atlas of the Human Brain and Spinal Cord” (Fix, J., 2nd ed.). It is strongly recommended that your laboratory group use your atlas in each laboratory session. Moreover, it will be of value in all phases of this course to help you in understanding the three-dimensional anatomy of the human nervous system.

There is also an additional item that should be downloaded from eCampus. This includes a set of annotated Neuroscience slides (Neuroscience Lab Manual Supplement). The file of labeled slides contains representative spinal cord and brainstem sections taken from your slide set.

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NOTE: UNDER NO CIRCUMSTANCES ARE THE BRAIN SPECIMENS TO BE REMOVED FROM THE LABORATORY AT ANY TIME.

To assist you in learning the neuroanatomical structures discussed in this laboratory manual, there is an “Objectives” statement at the beginning of each laboratory section. Further, the important structures and/or concepts for each laboratory are in bold print or are underlined. In addition, questions pertinent to the area being studied are interspersed throughout each laboratory session in italicized print.

For examination purposes, the location of neuroanatomical structures will be assessed from lecture and the laboratory manual. Lecture handouts and the laboratory manual are considered the ultimate authority in correctly identifying structures and the determination of correct answers for exam questions. As such, contradictory information obtained from external resources (other atlases, websites, annotated slides from your preceding classmates) does not apply.

 Animations – For many laboratory assignments in this manual, links to video animations are provided. These animations depict the anatomical relationships between important (bold) structures that will assist in your understanding of the three-dimensional organization of the brain.

 Laboratory Demonstrations -- There will be laboratory demonstrations during most laboratory sessions. These will consist of models and/or pre-dissected wet specimens. Since these demonstrations will be "fair game" for laboratory practical exams, it is recommended that you take the time to view them when they are displayed during normal laboratory hours.

 Neurorounds – For some laboratory sessions, case studies will be used to integrate lecture and lab material so as to illustrate their clinical implications. These case studies will be administered using two different formats: 1) active learning presentation/discussion in lab; or 2) self-study, written with corresponding questions. Active learning case studies (#1) will be presented by faculty usually during the last 30-40min of lab. Students will be expected to review the lab and associated lecture in advance so as to enable participation in

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the discussion and provide “team-based” responses to questions on pathways and clinical correlates related to the case. Self-study written cases (#2) are provided at the end of corresponding labs. Students should review the case study in advance and begin working on the case during the lab. Each case contains questions about related pathways/function and specific clinical findings. Faculty will be available during the lab to discuss/clarify clinical findings and other aspects of the case but not provide answers to the questions. Answers to these questions will be posted ~2 days after the lab on eCampus. Although there are no specific performance-type grades for the active learning or self- study written case studies, the content of these cases will be covered in some fashion on either the practical or written exams and related questions should be expected on the NBME and USMLE exams.

Finally, it will be useful to read through each laboratory assignment, using your brain atlas, prior to the laboratory session. This should help make both lecture and laboratory material easier to comprehend.

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GROSS ANATOMY OF THE BRAIN

Learning Objectives: At the end of the laboratory session students will be able to: 1. Utilize their developing anatomical vocabulary to locate and identify external and internal features of the brain. 2. Describe the directional terminology of the central nervous system (CNS) and the location where this terminology axis shifts. 3. Discuss the major subdivisions of the brain and key anatomical structures located within these regions. 4. Demonstrate gray and white matter and relate the specific cellular parts (cell body vs. axons/dendrites) constituting the two. 5. Identify the lobes of the brain, landmarks demarcating their separation and general features of each. ______

Before we begin, it is important to understand the directional terminology or nomenclature as it relates to the brain. Below is a diagram (Fig. 1) to assist you in understanding this terminology. It is important that you understand it, since we will be using this terminology in lecture and laboratory throughout the course to describe the relative locations of various CNS structures.

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In this laboratory session, we will be studying what could be called "lump and bump" anatomy. That is, we will be identifying and briefly discussing the gross external and internal anatomy of the brain. The purpose of this laboratory is simply to acquaint you with the appearance and location of structures that we will be revisiting in detail as the course progresses. These structures will also be used as landmarks to locate and identify other anatomical features of the brain. Use your atlas to assist in the identification of the structures listed in this and all future laboratory sessions.

Whole and Half Brain Specimens

We will begin by identifying the features of the major subdivisions of the brain, using the whole and half brain specimens in your brain buckets. The brain is organized from rostral to caudal as follows: 1) telencephalon, 2) diencephalon, 3) mesencephalon [midbrain], 4) metencephalon [pons], 5) myelencephalon [medulla oblongata] and 6) cerebellum. Items 2 through 5 above are collectively called the brainstem.

The telencephalon is composed of the cerebral hemispheres and portions of the basal ganglia. The latter will be studied in a subsequent laboratory session. The cerebral hemispheres are the large, external, convoluted mantles of nervous tissue that overlie the brainstem. The superficial region of the cerebral hemispheres is composed of gray matter. Immediately deep to the gray matter is a relatively thick layer of white matter. To confirm this, look at selected horizontal and coronal sections. How does this compare to what is seen in spinal cord? The cerebral hemispheres are divided into right and left halves at the midline by the prominent interhemispheric (longitudinal cerebral) fissure. The raised areas, or convolutions, on the surface of the cerebral hemispheres are called gyri (sing. - gyrus). The corresponding grooves or depressions are collectively called sulci (sing. - sulcus). The larger, deeper grooves are usually referred to as fissures.

Each cerebral hemisphere is divided into lobes (Fig. 2). Observe the brain from a lateral view. From this perspective, it resembles a catcher's mitt with the "thumb" portion located in a ventrolateral position. This "thumb" portion is the temporal lobe. It is separated from the more dorsal aspect of the brain by a deep groove

Neuroscience Laboratory Manual 7 called the lateral (Sylvian) fissure. Locate the horizontally arranged superior, middle and inferior temporal gyri. Immediately dorsal to the lateral fissure is the frontal lobe, which extends from the rostral pole (end) of the brain caudally to the central sulcus (of Rolando). This sulcus separates the frontal lobe from the parietal lobe. Two important gyri lie immediately rostral (precentral gyrus) and caudal (postcentral gyrus) to the central sulcus. Immediately rostral to the precentral gyrus is the precentral sulcus. Rostral to the precentral sulcus lie three horizontally arranged gyri. These are, from dorsal to ventral, the superior, middle and inferior frontal gyri.

The caudal extent of the parietal and temporal lobes is delineated by an imaginary line drawn from the parietooccipital sulcus dorsally to the preoccipital notch ventrally (Fig. 2). The remaining region of brain from the "imaginary line" caudally is called the occipital lobe. The caudal-most extent of the occipital lobe is called the occipital pole. The parietal lobe is separated from the temporal lobe by drawing an imaginary horizontal line that extends caudally from the Sylvian fissure to the previous "imaginary line" between the parietooccipital sulcus to the preoccipital notch.

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The caudal end of the Sylvian fissure turns dorsally to terminate and is surrounded by the supramarginal gyrus. Deep to the Sylvian fissure lies a region of cortex called the insula (insular cortex [lobe]). Identify this structure on your horizontal and coronal brain slices. In some instances, the insula can be seen on the whole or half brain by GENTLY separating the frontal and temporal lobes. If you are unable to see the insula on your whole or half brain specimens, this structure can be seen clearly on demonstration. DO NOT FORCE THE LOBES APART BY TEARING BRAIN TISSUE.

Now turn the whole brain over to view the ventral surface. Beginning on the lateral aspect of the temporal lobe and working medially, find the occipitotemporal (fusiform) gyrus, and parahippocampal gyrus. Near the rostral end of the parahippocampal gyrus is a small, medially directed protuberance of cortical tissue called the uncus.

To complete our survey of the cerebral hemispheres, observe the medial surface of the half brain. Find the central sulcus as it winds its way onto the dorsal aspect of the medial surface of the cerebral cortex to terminate. Surrounding the termination of the central sulcus is the paracentral lobule, which is a fusion of pre- and postcentral gyri. Immediately caudal to the paracentral lobule is a region of cortex called the precuneus. It is bounded caudally by the vertically oriented parietooccipital sulcus. From the occipital pole, the calcarine sulcus runs rostrally to join the parietooccipital sulcus. The calcarine sulcus divides the occipital lobe into a dorsal region called the cuneus and a ventral region called the lingula.

Located at the approximate center of the medial surface of the half brain is a sickle shaped structure, the corpus callosum. This is a massive interhemispheric nerve fiber pathway that provides reciprocal communication between the two cerebral hemispheres. It is divided into parts from rostral to caudal as follows: rostrum, genu, body and splenium. The corpus callosum is surrounded by cerebral cortex that contributes to a structure we will study in detail later called the limbic lobe.

Hanging from the ventral surface of the corpus callosum is a membrane called the septum pellucidum. Along the free ventral border of the septum pellucidum is a fiber bundle called the fornix. Follow the fornix as it arches rostrally. In the region just rostral to where the fornix dives out of site is a small interhemispheric fiber

Neuroscience Laboratory Manual 9 bundle called the anterior commissure. This structure interconnects portions of the temporal lobes and components of the olfactory system. Immediately rostral and ventral to the anterior commissure is a thin membrane called the lamina terminalis. This structure spans the midline. As such, it has been cut on your half brain specimens. Follow the lamina terminalis ventrally to the optic chiasm. Note that the optic chiasm is continuous with the optic nerves (CN II) rostrally and the optic tracts caudally. Just ventral to the optic chiasm is the infundibulum (pituitary stalk). Arching caudally from this structure is another thin sheet of tissue called the tuber cinereum, which leads to the paired mammillary bodies. (NOTE: since you are viewing the half brain, there will be only one mammillary body). The region of brain roughly between the lamina terminalis and the caudal aspect of the mammillary bodies is the hypothalamus. It is separated from the dorsally located, egg-shaped thalamus by a rostrocaudal groove called the hypothalamic sulcus.

On the half brain, the medial surface of the thalamus typically reveals a severed medial protrusion of thalamic tissue. This is the remnants of the massa intermedia (interthalamic adhesion) which, when present, connects the left and right thalami. The hypothalamus, thalamus, habenula and pineal gland constitute the major portion of the diencephalon, the most rostral extent of the brainstem. Another structure, the subthalamus, is also a part of the diencephalon and will be seen at a later date. It should be noted at this point that there is a space between diencephalic structures on the left and right sides. This centrally located space is the third ventricle.

At the juncture of the thalamus and midbrain (mesencephalon), there is a ventral flexure of the brainstem. This is called the cephalic flexure. Proceeding caudally (inferiorly) from the mammillary body on the half brain, there is a relatively deep longitudinal furrow in the midline. This is the interpeduncular fossa. Just lateral to the interpeduncular fossa, observe one of the paired cerebral peduncles (crus cerebri). These are important structures that carry descending nerve fibers from the cerebral cortex to other regions of the brain and spinal cord. If intact, the oculomotor nerve (CN III) can be seen emerging from the medial surface of the cerebral peduncle. On the dorsal surface of the midbrain lie two rounded protuberances. The more rostral one is the superior colliculus, which is associated with the visual system. The more caudal one is the inferior colliculus, which is associated with the auditory system. On the whole brain, each of these colliculi are Neuroscience Laboratory Manual 10 paired structures (i.e., two superior colliculi, two inferior colliculi [see demonstration]) and are collectively referred to as the corpora quadrigemina or tectum of the midbrain. Separating the tectum and the more ventrally located tegmentum of the midbrain is a small rostro-caudal channel called the cerebral aqueduct (of Sylvius).

The large ventral convexity caudal to the cerebral peduncles is the pons (metencephalon). If an imaginary line is drawn from the inferior aspect of the inferior colliculus ventrally to the junction of the cerebral peduncles with the pons, this roughly represents the caudal extent of the midbrain. Follow the pons dorsolaterally. Just caudal to where the trigeminal nerve (CN V) emerges, there is a thick band of nerve fibers connecting the pons with the overlying cerebellum. This is the middle cerebellar peduncle (brachium pontis). (NOTE: there are also inferior and superior cerebellar peduncles that can be seen on demonstration). The "potbellied" pons ends caudally where it meets the medulla (myelencephalon) at the ponto-medullary junction. This can be seen as a horizontal groove from which the abducens (CN VI), facial (CN VII) and vestibulocochlear (CN VIII) nerves emerge from medial to lateral respectively. The lateral-most portion of this groove where CNs VII and VIII emerge is called the cerebellopontine angle. This is where the pons, medulla and cerebellum join together. The large cerebellum can be seen sitting astride the dorsal surfaces of the pons and medulla. Two thin sloping membranes (superior & inferior medullary vellae) usually can be seen stretching between the cerebellum and the dorsal surface of the brainstem. The superior medullary velum (more rostral) and the inferior medullary velum (difficult to see but stretches from the inferior aspect of the cerebellum to the medulla) form a triangular space with the pons and medulla, called the fourth ventricle.

The ventral surface of the medulla is best seen on the whole brain. On either side of the midline on the medulla, just caudal to the ponto-medullary junction, is a pair of rounded ridges. These are the pyramids and are caused by the underlying pyramidal (corticospinal) tract. Immediately lateral to the pyramids at this level are a pair of egg-shaped swellings called the inferior olives. The groove between the inferior olive and the pyramid on each side is the preolivary sulcus. Filaments of the hypoglossal nerve (CN XII) can be seen emerging from this sulcus. Dorsolateral to the inferior olive is another groove called the postolivary sulcus from which the

Neuroscience Laboratory Manual 11 glossopharyngeal (CN IX), vagus (CN X) and the bulbar portion of the spinal accessory (CN XI) nerves emerge.

Identify the following structures on the whole brain: lamina terminalis, optic nerves, optic chiasm, optic tracts, infundibulum, tuber cinereum, mammillary bodies, cerebral peduncles, interpeduncular fossa, CN III, pons, CN V, VI, VII and VIII, middle cerebellar peduncles.

ANIMATIONS

 Cerebral cortex - lobes (BrainlobesX, BrainlobesY)  Brainstem

DEMONSTRATIONS

 Dorsal brainstem showing: thalamus, superior and inferior colliculi, trochlear nerve (CN IV), superior, middle and inferior cerebellar peduncles, fourth ventricle. Use Fig. 3 below to assist in identifying the above structures on the demonstration.

Neuroscience Laboratory Manual 12  Half brain (lateral view) showing: central sulcus, lateral fissure, precentral and postcentral gyri, insula, paracentral lobule, angular gyrus, supramarginal gyrus.

 Half brain (medial view) showing: paracentral lobule, parietooccipital sulcus, calcarine sulcus, lingula, cuneus, corpus callosum (all parts), cingulate gyrus.

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MENINGES

Learning Objectives: At the end of the laboratory session students will be able to: 1. Review the layers of meninges as learned in Gross Anatomy. 2. Locate and be able to name the subarachnoid cisterns which surround the brain and spinal cord. ______

The meninges consist of 3 concentric membranous layers of tissue that surround the brain and spinal cord.

Dura mater -- The outermost, thick, fibrous layer of meninges is called the dura mater. As many of you know from gross anatomy, the dura mater is made up of 2 layers (an inner [meningeal] and outer [endosteal/periosteal] layer) that are typically fused together. The outer layer is, in turn, fused to the inner surface of the skull. As such, there will not be any dura mater on the brains in your buckets. It should be noted that the periosteal layer of dura mater passes through the foramen magnum to fuse with the periostium on the external surface of the skull. Consequently, the only layer of dura mater covering the spinal cord is the meningeal layer. Since the dura mater is intimately involved in the drainage of blood from the brain, there will be a demonstration of the dura mater and its reflections within the skull later in this laboratory session during our review of the blood supply to the CNS.

Arachnoid mater -- This intermediate layer of the meninges usually remains at least partially intact on the surface of the brain after it is removed from the skull. On the whole or half brain, look on the lateral surfaces of the cerebral hemispheres. If the arachnoid mater is present, it will appear as a transparent membrane that spans the sulci and fissures of the cerebral cortex. Immediately deep to the arachnoid mater lies an important region called the subarachnoid space. It contains: 1) cerebrospinal fluid and 2) the major blood vessels of the brain. Using a blunt probe, slip the tip through an existing gap or tear in the arachnoid mater and gently elevate Neuroscience Laboratory Manual 14 the arachnoid layer to demonstrate the subarachnoid space. Over most of the surface of the brain, the subarachnoid space is relatively shallow. However, in those regions where there are wide and/or deep depressions on the surface of the brain, the arachnoid layer stretches across these depressions, resulting in enlargement of the subarachnoid space. These enlargements are called subarachnoid cisterns.

Using both the whole and half brains, four of the major cisterns can be demonstrated. On the ventral surface of the midbrain, locate the cerebral peduncles. The depression in the midline between the cerebral peduncles is the interpeduncular fossa. If the arachnoid is present, it will be seen stretching across the interpeduncular fossa between the cerebral peduncles. The space formed between the floor of the fossa and the overlying arachnoid layer is called the interpeduncular cistern. Immediately caudal to the cerebral peduncles lies the convex protuberance of the ventral pons. The pontine cistern lies immediately ventral to the pons and extends caudally to enlarge and terminate at the junction of the pons and medulla (ponto-medullary junction). Now turn the brains over to view the dorsal surface. The two cisterns on this surface of the brain lie either immediately rostral or caudal to the cerebellum. The more rostral of these, the superior cerebellar (quadrigeminal) cistern is best seen on the medial surface of the half brain. It is roughly bounded by the splenium of the corpus callosum superiorly, the superior and inferior colliculi (corpora quadrigemina) ventrally and the superior surface of the cerebellum inferiorly. The remaining cistern of note, the cerebellomedullary cistern (cisterna magna), lies at the inferior surface of the cerebellum and the dorsal surface of the medulla where the arachnoid layer reflects from the cerebellum to the medulla. Use your blunt probe to gently explore the extent of these cisterns. It is important to note that another clinically important cistern is located immediately caudal to the termination of the spinal cord. What is the name of this cistern? At what vertebral level does the spinal cord terminate?

Pia mater -- This innermost layer of the meninges is, for the most part, closely adhered to the surface of the brain and spinal cord. As such, it is difficult to demonstrate with the naked eye. At the microscopic level, small blood vessels that penetrate the parenchyma (substance) of the brain are surrounded by pial sleeves

Neuroscience Laboratory Manual 15 that penetrate variable distances into the brain. There are two obvious occasions where the pia mater separates from the surface of the CNS and can be readily seen. What is the site of each of these pial separations and what are they called? (Think Gross Anatomy).

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BLOOD SUPPLY TO THE BRAIN AND SPINAL CORD

Learning Objectives: At the end of the laboratory session students will be able to: 1. Identify the main arteries supplying the brain, brainstem and spinal cord. 2. Describe the areas of the central nervous system supplied by specific arteries. 3. Name the component parts and function of the Circle of Willis. 4. Discuss the general level of dysfunction that would result from compromise of any of the described vessels. 5. Identify watershed areas which correspond to border zones between the territories of two principle arteries. 6. Review the dural venous sinuses and trace the major veins that drain the CNS. ______

Vascular injury and/or vascular disease constitute a major source of nervous system pathology. The CNS is critically dependent upon glucose and oxygen, neither of which is stored in significant amounts by the CNS. Consequently, should the blood supply to the CNS be disrupted, even for a relatively brief period, destruction of CNS parenchyma occurs with the resultant permanent loss of function, or death.

Brain -- The blood supply to the brain is typically described as being provided by two arterial systems: an anterior system which is composed of the internal carotid arteries and their branches; and the posterior (vertebral - basilar) system, composed of the vertebral arteries. These two systems are demonstrated in Fig. 4 below.

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Posterior System -- Using the whole brain, turn it over to view the ventral surface. Note the paired vertebral arteries ascending on the ventrolateral surface of the medulla. As you may recall, the vertebral arteries arise from the subclavian arteries and ascend through the foramina transversaria of cervical vertebrae C-6 through C-1 to enter the skull through the foramen magnum. Typically, the vertebral arteries fuse at the midline at the level of the ponto-medullary junction to form the unpaired basilar artery. Before the vertebral arteries fuse, they give rise to three pairs of arteries. The first of these are the posterior spinal arteries that descend on the dorsal surface of the spinal cord just medial to the dorsal spinal roots. Since the posterior spinal arteries are typically the first to arise from the vertebral arteries as they traverse the foramen magnum, they are often absent due to the level where the vertebral arteries were cut when the brain was removed from the skull. The second branches are the posterior inferior cerebellar arteries (PICA) which wrap around the medulla to ramify on the inferior surface of the cerebellum. As these arteries wrap around the medulla to gain access to the

Neuroscience Laboratory Manual 18 cerebellum, they send small branches to supply the lateral region of the medulla. Occasionally, the posterior spinal arteries may arise from PICA. The anterior spinal arteries, which descend to fuse as a single artery at the midline on the ventral surface of the medulla, are usually the last branches from the vertebral arteries before they fuse to become the basilar artery. Shortly after the basilar artery is formed, it gives rise to the paired anterior inferior cerebellar arteries (AICA), which ramify on the ventral surface of the cerebellum. As the basilar artery ascends on the ventral surface of the pons, it gives rise to many small pontine arteries. Just prior to terminating, the basilar artery gives rise to the paired superior cerebellar arteries, which wrap around and supply the midbrain on their way to ramify on the superior surface of the cerebellum. The basilar artery terminates at the level of the midbrain by dividing into the large, paired posterior cerebral arteries. At this time, look for the oculomotor nerve (CN III) which acts as a landmark by emerging between the posterior cerebral and superior cerebellar arteries.

Anterior System -- After entering the skull through the carotid canal each internal carotid artery passes through the cavernous sinus, then turns 180° caudalward to gain access to the ventral surface of the brain. It is at this point that the internal carotid arteries are cut to remove the brain from the skull. On the ventral surface of the whole brain, find the severed ends of the internal carotid arteries as they lie just lateral to the optic chiasm. There are four branches that can be readily seen arising from the internal carotid arteries: two from the main trunk and two terminal branches. The first small branch is the posterior communicating artery. This artery passes caudally to anastomose with the posterior cerebral artery. The next branch is the anterior choroidal artery. This small artery passes caudally to disappear deep to the temporal lobe. As the name implies, this artery supplies blood to the choroid plexus (and other structures). Shortly after the internal carotid artery gives rise to the anterior choroidal artery, it divides into its two terminal branches, the anterior and middle cerebral arteries. The latter is larger and considered by some to be the continuation of the internal carotid artery. Immediately distal to the origin of the anterior choroidal artery, a variable number (2-5) of small threadlike arteries can be seen arising from the middle cerebral artery and immediately diving into brain parenchyma. These are the lateral striate (lenticulostriate) arteries. Although small, these arteries supply critical areas of the brain. The middle cerebral artery continues laterally to dive into the lateral sulcus (Sylvian fissure) deep to the Neuroscience Laboratory Manual 19 rostral pole of the temporal lobe. Branches of the middle cerebral artery can be seen on the lateral surface of the brain as they emerge from the lateral sulcus.

On the ventral surface of the whole brain, the anterior cerebral arteries can be seen coursing medially to pass dorsal (deep) to the optic nerves. As they approach the midline just rostral to the optic chiasm, these arteries are joined together by an anastomotic channel called the anterior communicating artery. Both anterior cerebral arteries then disappear by diving into the interhemispheric fissure, each one supplying ipsilateral structures on the medial and dorsal surface of the brain.

On your half brains, follow the course of an anterior cerebral artery as it courses along the rostral and dorsal surfaces of the genu of the corpus callosum. At this point, the anterior cerebral artery typically divides into its two terminal branches, the pericallosal and callosomarginal arteries. The pericallosal artery runs caudally along the dorsal surface of the body of the corpus callosum. The callosomarginal artery takes a more dorsal path caudally by running in or near the cingulate sulcus. Note the branches of these arteries and the general areas they supply.

Now turn your attention back to the ventral surface of the whole brain. The posterior cerebrals, posterior communicating, internal carotids, anterior cerebrals and anterior communicating arteries form an arterial circle (of Willis) at the base of the brain surrounding the hypothalamus, infundibulum and optic chiasm. You may be able to see many small arteries arising from the internal surfaces of the circle of Willis. They are generally referred to as central or ganglionic arteries. The circle of Willis is clinically important in that if a blood vessel should be occluded on one side of the circle, blood can be shunted to bypass the obstruction. However, since this arterial circle is variable (i.e., branches small or missing), this is not an iron-clad rule.

Another issue to consider is that although there is some overlap along the periphery of the territory for adjacent arteries supplying the brain, these arteries are functionally "end" arteries, in that they are the sole blood supply to the vast majority of a given area of brain. Consequently, permanent or prolonged occlusion of a single artery results in necrosis of the brain area supplied by that artery.

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Venous Return -- Unlike the arterial supply to the brain, venules emerge from the substance of the brain as fine pial plexuses that coalesce to form larger visible veins that reside in the subarachnoid space. A good example of this can be seen on the surface of the cerebral hemispheres. An exception to this general rule can be seen on the medial surface of a half brain. Look along the dorsomedial aspect of the thalamus on a half brain. A relatively large vein can usually be seen running in a rostrocaudal direction. This vein drains deeper brain structures and is called the internal cerebral vein. As this vein reaches the subarachnoid space at the caudal aspect of the thalamus, you may be able to see another vein joining the internal cerebral vein from the ventral side. This is the basal vein (of Rosenthal). If you do not have this vein on your specimen, it can be seen on demonstration. After it is joined by the basal vein, the internal cerebral vein becomes the great cerebral vein (of Galen). NOTE: the paired (i.e., left and right) internal cerebral and basal veins are tributaries of the single great cerebral vein. Into what venous structure does the great cerebral vein empty? What is the name of the subarachnoid compartment where the above veins join together?

Although the larger veins within the subarachnoid space on the surface of the brain generally run in parallel with their arterial counterparts, these veins soon depart from the arteries to drain into specialized endothelium-lined venous channels between the meningeal and periosteal layers of the dura mater called dural venous sinuses. These sinuses are formed in certain regions of the cranial cavity where the inner (meningeal) layer of dura mater separates from the outer (periosteal) layer to form: 1) horizontal septae that divide the cranial cavity into compartments, or 2) vertical septae that occupy the fissures between the left and right cerebral and cerebellar hemispheres.

Using any gross anatomy text or atlas, identify and note the location of the following dural septae and major dural venous sinuses: falx cerebri, superior sagittal sinus, inferior sagittal sinus, tentorium cerebelli, tentorial notch (incisure), straight sinus, confluence of sinuses, transverse sinus, sigmoid sinus and cavernous sinus. What subdivision of the brainstem occupies the region within the tentorial notch? At this time, you should review the direction of normal blood flow in these dural venous sinuses. What major vein receives blood from the sigmoid sinus?

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Spinal Cord -- The spinal cord has a longitudinal and segmental blood supply. The longitudinal supply is provided by the single anterior and, if present, paired posterior spinal arteries arising from the vertebral arteries. However, these small arteries alone are only sufficient to supply upper cervical segments. Consequently, the primary source of spinal cord blood supply is provided by segmental arteries at cervical, thoracic and upper lumbar levels of the vertebral column. These arteries gain access to the spinal cord through intervertebral foramina where they reinforce the longitudinal supply through anastomotic channels.

ANIMATION

 Brain arterial systems

DEMONSTRATIONS

 Skull showing dural reflections and venous sinuses: falx cerebri, superior sagittal sinus, inferior sagittal sinus, tentorium cerebelli, tentorial notch (incisure), straight sinus, confluence of sinuses, transverse sinus.

 Ventral surface of whole brain showing blood supply: Identify blood vessels as labeled in Fig. 4 (p. 18) of this laboratory exercise.

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CSF AND VENTRICLES OF THE BRAIN

Learning Objectives: At the end of the laboratory session students will be able to: 1. Identify and locate all parts of the ventricular system of the brain. 2. Identify the brain structures that form the walls/boundaries of the various parts of the ventricular system. 3. Trace the normal flow of CSF through the ventricles and the general consequences of ventricular system blockage. ______

The brain is not a solid mass of nervous tissue. There are four interconnected cavities, called ventricles, deep within the brain. The two lateral ventricles are located within the cerebral hemispheres. The third ventricle is situated in the midline between the left and right portions of the thalamus and hypothalamus. The fourth ventricle is located between the cerebellum dorsally, and the pons and medulla ventrally. Each ventricle contains structures called choroid plexuses, which produce cerebrospinal fluid (CSF). The normal flow of CSF within the ventricular system is as follows: lateral → third → fourth. After it flows through the ventricles, it then gains access to the subarachnoid space through small foramina in the fourth ventricle. The CSF then percolates throughout the subarachnoid space surrounding the brain and spinal cord to eventually empty into the venous system. In addition to supporting and protecting the brain, CSF is important in the metabolic processes of the brain. The CSF also serves as an important diagnostic tool for a variety of neurological problems, and can be aspirated for analysis. It is critical that the CSF has unobstructed flow through the ventricular system of the brain and into the subarachnoid space. If blockage should occur, there will be a subsequent expansion of "upstream" ventricles (hydrocephalus), causing compression of surrounding brain tissue.

Half Brain; Horizontal and Coronal Sections

Observe the medial surface of your half brain specimen. Find the thalamus and hypothalamus. The area between (medial to) these structures and their Neuroscience Laboratory Manual 23 contralateral counterparts is the third ventricle. Find the anterior commissure and the rostral pole of the thalamus. Between these structures is a small hole called the interventricular foramen (of Monro). There are two of these foramina, one on each side. They interconnect the lateral ventricles with the third ventricle. If present, the choroid plexus can be seen hanging from the roof of the third ventricle. At the caudal end of the thalamus, the third ventricle narrows into a small passageway, the cerebral aqueduct (of Sylvius), which courses through the midbrain to open into the fourth ventricle. The fourth ventricle is continuous caudally with the central canal of the spinal cord. Attempt to find the choroid plexus in the fourth ventricle. It is from the fourth ventricle that the CSF enters the subarachnoid space. It does so by passing through: 1) a single midline foramen (foramen of Magendie) located at the caudal extent of the fourth ventricle where the inferior medullary velum contacts the medulla, and 2) two lateral foramina (foramina of Luschka) located at the lateral extremes of the fourth ventricle. The foramina of Luschka can be found by GENTLY insinuating the tip of your blunt probe into the lateral reaches of the fourth ventricle. If you have done this correctly, the tip of the probe will pass through the foramen of Luschka to appear externally in the cerebellopontine angle. It is common for the choroid plexus of the fourth ventricle to extend through the foramina of Luschka to reside in the subarachnoid space. Look in the region of the cerebellopontine angle for tufts of this structure as it emerges.

The lateral ventricles are located in the cerebral hemispheres. They can be viewed in their entirety by using both horizontal and coronal brain slices. Using your brain atlas, begin at the dorsal aspect of the horizontally sliced brain and remove slices, observing both surfaces of each slice, until the lateral ventricles are exposed. Note that the fibers of the corpus callosum form the roof, as well as the anterior and posterior boundaries of the lateral ventricles. Identify the genu, body and splenium of the corpus callosum. Find the choroid plexus within the lumen of the lateral ventricles and third ventricle. Identify the frontal (anterior) horn, body and occipital (posterior) horn of the lateral ventricles. Note the rounded mass that forms the lateral boundary of the frontal horns. This is the head of the caudate nucleus, a component of the basal ganglia. Find the thalamus, septum pellucidum and fornix, and determine their spatial relationships to the lateral ventricles. As you progress from dorsal to ventral, there is a region near the caudal end of the

Neuroscience Laboratory Manual 24 lateral ventricles where the body, occipital horn and temporal (inferior) horn meet. This is called the trigone (atrium) of the lateral ventricle. Follow subsequent sections ventrally into the temporal horn.

Find a horizontal section similar to that in the Fix Atlas: Plate 56 (p. 112) and identify the interventricular foramina (of Monro). As previously stated, these two foramina are the openings from the lateral ventricles into the centrally located third ventricle. Just lateral to each of these foramina is a "V" shaped region of white matter called the internal capsule, an important bidirectional pathway between the cortex and the brainstem and spinal cord. The apex of each "V" is called the genu of the internal capsule. Each genu is directed medially and points at the interventricular foramen on each side, thus serving as a landmark. The genu is continuous with the anterior and posterior limbs of the internal capsule.

Using your coronal brain slices and your brain atlas, identify the same structures you found in the horizontal sections. Compare and contrast these structures as they appear in horizontal and coronal section. The purpose of this important exercise is to begin to appreciate and understand the three dimensional anatomy of the brain, which is critical if you are to be successful in this block.

NEURORADIOLOGY

You should now have a basic understanding of the gross anatomy of the brain. If this assumption is correct, you should have little difficulty transferring this knowledge to interpret the variety of radiologic techniques that are used to visualize the various parts of the brain.

Using your Neuroscience slide set, look at slide 45. This is a mid-sagittal section of the brain as visualized by magnetic resonance imaging (MRI). This particular MRI is a T1 weighted image. What are the visual characteristics of a T1 weighted MRI of the brain such as the one seen on this slide? Identify the following brain structures/regions on this slide with the help of your half brain specimens: corpus callosum (all portions), cingulate gyrus, fornix, thalamus, cerebral aqueduct (note arrowheads), subarachnoid cisterns (interpeduncular, pontine, superior cerebellar, cisterna magna), parietooccipital sulcus, calcarine fissure, cuneus, lingula, cerebellum, fourth ventricle, medulla, pons, midbrain, superior and

Neuroscience Laboratory Manual 25 inferior colliculi, mammillary body, hypothalamus, optic chiasm, optic nerve and interventricular foramen of Monro.

Slide 46 is an MRI (T1 weighted) of the brain in coronal section. Using a similar coronal slice from your brain specimens as an aid, identify the lateral ventricles, third ventricle, thalamus, body of the corpus callosum, lateral fissure, insula, temporal lobe and interhemispheric fissure.

Slide 47 is a T1 weighted MRI taken in the horizontal plane. Using a similar horizontal slice from your brain specimens as an aid, identify the frontal horns of the lateral ventricles, third ventricle, head of the caudate, thalamus, internal capsule (all parts), trigone (atrium) of lateral ventricle, splenium of corpus callosum, lateral fissure and insula.

Slide 51 shows two T2 weighted horizontal images of the brain. In the left image, note the occipital horn of the lateral ventricle on the left side of the slide. Is this the patient’s left side? Which of the two images is higher (more superior)? The midbrain and the middle and posterior cerebral arteries can also be seen. Note the location and orientation of the cerebral peduncles. Verify this by comparing this image with a similar horizontal section from your brain specimens. The right image shows the frontal horns of the lateral ventricles, third ventricle, and trigone (atrium) of the lateral ventricles. How does the appearance of the ventricles on this slide differ from that seen in a T1 weighted image? Slide 65 is a similar MRI, showing anterior, middle and posterior cerebral arteries as well as mammillary bodies, third ventricle, rostral midbrain and uncus. Is this a T1 or T2 weighted image? Look at slide 64. Is this section rostral or caudal to slide 65? What blood vessels can be seen in this view?

ANIMATIONS DEMONSTRATIONS

 Ventricles (midline)  Cast of human ventricular  Ventricles (trans) system.  Ventricles (X, X2, Y)

Neuroscience Laboratory Manual 26

INTRODUCTION TO THE MACROSCOPIC ANATOMY OF THE NEURAXIS

Learning Objectives: At the end of the laboratory session students will be able to: 1. Be able to quickly identify representative levels of the neuraxis, including the salient internal and external features of these representative levels as viewed on the stained, macroscopic sections in your slide sets. 2. Attempt to discern the plane-of-section of each of the slides (horizontal, coronal, sagittal, etc.). 3. Distinguish cytological staining differences between collections of cell bodies (i.e., nuclei and/or ganglia) versus nerve fibers/tracts. ______

As part of the learning aids in the neuroscience laboratory, you have been provided with a set of slides showing the macroscopic anatomy of the human brain and spinal cord. The slides are arranged in ascending order, beginning with the sacral spinal cord (slide #1) and ending with telencephalic structures. Those sections of the neuraxis from spinal cord through midbrain are cut in horizontal section. Because of the flexure of the brain between the diencephalon and midbrain, subsequent slides show brain sections cut in varying planes between horizontal and coronal. The purpose of the following exercise is to familiarize you with the "typical" appearance of the various levels of the spinal cord and brainstem so that you can instantly recognize these levels when you see them. Make extensive use of your Fix brain atlas, and the supplementary labeled slides (available on eCampus and at the back of this laboratory syllabus), to assist you in the identification of internal and external landmarks at these various levels.

Spinal Cord (slides 1-5)

Observe slide 1. This is a cross section of the sacral spinal cord. The dorsal surface of this section, as well as subsequent sections of spinal cord and brainstem through the midbrain, is located at the top of the slide. The vast majority of the sections on

Neuroscience Laboratory Manual 27 the slides are stained with one of two types of nerve fiber stains. Slide 1 is stained by the luxol fast blue method for myelinated nerve fibers, and counterstained with hematoxylin and eosin to reveal neuronal cell bodies. Note the dark blue staining of the white matter (nerve fibers) around the periphery, and the relative absence of blue staining in the centrally located gray matter, which contains neuronal cell bodies. The butterfly shaped gray matter is divided into dorsal (posterior) and ventral (anterior) horns with an intervening lateral horn. The latter will be seen more clearly in subsequent sections. Note the gray commissure that connects the left and right sides of the gray matter. Observe the small purple dots scattered throughout the ventral horn. These are the ventral motor horn cells that give rise to the majority of axons within the ventral roots. Observe the arched pink region near the top of the dorsal horn. This is the substantia gelatinosa, an important sensory relay nucleus. The gray matter immediately ventral to the substantia gelatinosa contains the less distinct nucleus proprius (proper sensory nucleus). The white matter dorsal to the substantia gelatinosa is Lissaur's tract, an intersegmental spinal pathway. The white matter can be roughly divided into funiculi (columns) based on their position in the spinal cord. The dorsal funiculus is located between the dorsal horns of the gray matter. The lateral funiculus occupies the region between the dorsal and ventral roots. The ventral funiculus lies between the midline and the emergence of the ventral roots. Immediately ventral to the gray commissure is the anterior white commissure, which contains nerve fibers that cross the midline. The prominent dorsal and ventral median fissures serve to vertically divide the white matter at the midline. Each of the above funiculi contain important ascending and descending nerve fiber tracts that will be identified at a later date. Note the single anterior spinal artery and the multiple posterior spinal arteries and their location immediately external to the pia mater.

Now look at slide 2. This is a cross section of the lower lumbar spinal cord stained with the Weil stain. This histological procedure stains the myelin of nerve fibers black. The gray matter (cell bodies) remains unstained with the exception of those regions where myelinated nerve fibers traverse it. Observe the large lateral projections of the ventral horns. What is the purpose of these lateral extensions? Why would you expect to see them at this spinal level? In slide 2, and all subsequent slides of the spinal cord (slides 3-5), identify all of the structures you found on slide 1.

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Slide 3 (upper lumbar) appears similar to slide 2. Dentate (denticulate) ligaments can be clearly seen in this section. What tissue layer comprises the dentate ligaments? What are their functions?

Slide 4 (thoracic) reveals the prominent intermediolateral gray (cell) column. What specific cell type is contained within this column? Why is the gray matter so small in the thoracic region?

Slide 5 is at the C-1 spinal level. Although it resembles the thoracic spinal cord, there are some distinct differences. The intermediolateral cell column has been replaced by the spinal accessory nucleus. How would the gray matter differ if this were a lower cervical section? In addition, at this level the substantia gelatinosa is replaced by the spinal nucleus of V (spinal trigeminal nucleus). A roughly circular region of white matter in the lateral funiculus near the base of the dorsal horn is separated into multiple fascicles. This is the lateral corticospinal tract, an important descending pathway which has just decussated (crossed the midline) at more rostral levels to assume its position within the lateral funiculus.

Compare the relative appearances of the spinal cord in slides 1 (sacral), 2 (lower lumbar), 3 (upper lumbar), 4 (thoracic), 5 (cervical) and be able to recognize and identify each level by listing their major differences.

Medulla (slides 7,12)

Slide 7 is a representative section of the caudal medulla. This level is occasionally referred to as the "closed" portion of the medulla, since it is caudal to the fourth ventricle and thus reveals a "closed" central canal surrounded by nuclei and fiber tracts. The prominent spinal nucleus of V can be seen. The dorsal column region now displays a nucleus (nucleus gracilis) on either side of the midline. What external feature reveals the location of these nuclei? The thick, black "X" at the midline ventrally is the decussation of the pyramids, a crossing of descending nerve fibers that will form the previously mentioned lateral corticospinal tracts seen in slide 5.

Slide 12 is a typical representation of the rostral medulla. This level is also called the "open" medulla because the central canal has "opened" to form the floor of the

Neuroscience Laboratory Manual 29 fourth ventricle. This level is immediately recognizable by the pyramids ventrally, the coiled appearance of the inferior olivary nuclei, the well-defined inferior cerebellar peduncles, fourth ventricle and overlying cerebellum. The medial lemniscus, an important ascending sensory pathway, can be seen in the midline sandwiched between the left and right inferior olivary nuclei. Also note the choroid plexus within the fourth ventricle and its extension through the foramina of Luschka to lie externally within the cerebellopontine angle. The inferior olivary nuclei cause an external bulge, the inferior olive. Immediately ventral and dorsal to the inferior olive are the pre- and post-olivary sulci, respectively. What cranial nerves emerge from each of these sulci?

Pons (slides 16,17,19)

Slide 17 is a cross section of the caudal 1/3 of the pons. The characteristic ventral convexity of the ventral pons can be clearly seen. Imbedded within this region are the dark stained fascicles comprising the pyramidal tracts, which are surrounded by the intervening light areas which are the pontine nuclei. Dorsal to the pyramidal tracts is the medial lemniscus. At this level, it is shaped like a handlebar mustache and forms the dorsal border of the ventral pons. It is located in a region of the pons called the pontine tegmentum, which extends dorsally to form the floor of the fourth ventricle. The large black areas forming the lateral boundaries of the pons at this level are the middle cerebellar peduncles (brachium pontis). In the pontine tegmentum just medial to the middle cerebellar peduncles, the fascicles of the facial nerve (CN VII) can be seen as they traverse the pons to emerge caudally at the cerebellopontine angle. Identify the above pontine structures on slide 16, where the superior, inferior and middle cerebellar peduncles can be seen simultaneously. Can you find the emerging fibers of the abducens nerve (CN VI) in this section? Compare these sections with slide 19 (rostral pons) where you should be able to identify the superior cerebellar peduncles, fourth ventricle, ventral pons, pyramidal tracts, and medial lemniscus.

Midbrain (slides 21,23)

All levels of the midbrain are characterized by the cerebral peduncles (crus cerebri) and interpeduncular fossa ventrally, the substantia nigra (the clear region

Neuroscience Laboratory Manual 30 immediately dorsal to the crus cerebri) and the medial lemniscus (dorsomedial to the substantia nigra).

The level of the inferior colliculus (slide 21) has unique characteristics, which include the decussation of the superior cerebellar peduncles, the nucleus of CN IV and the distinct nuclei of the inferior colliculi.

The level of the superior colliculus (slide 23) is characterized by the paired red nuclei, nuclear complex of the oculomotor nerve (CN III) and the emerging rootlets of CN III as they pass through the red nuclei to emerge from the midbrain along the walls of the interpeduncular fossa.

Diencephalon (slides 23,29)

In addition to midbrain, slide 23 also contains some of the caudal structures of the thalamus, a major subdivision of the diencephalon. These structures of the thalamus are the pulvinar and the medial and lateral geniculate bodies. Slide 29 reveals more of the nuclei of the thalamus, including two important sensory relay nuclei, the ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei, as well as the pulvinar. The mammillary bodies are also clearly seen. Midbrain structures such as the cerebral peduncles, substantia nigra and red nuclei are also present. Notice how the cerebral peduncles merge with the posterior limb of the internal capsule. Using your half brains, figure out the plane of section of slide 29.

NEURORADIOLOGY

Slide 52 is a midsagittal MRI through the cervical region. Identify the spinal cord, vertebral bodies and intervertebral disks. Note the abnormality in the spinal cord at C3-4 (herniated disk).

Slide 53 is a midsagittal MRI through the lumbar and upper sacral region. Find the subarachnoid space, intervertebral disks and termination of the spinal cord. Is this a T1 or T2 weighted image? Using your anatomical knowledge from Gross Anatomy, can you identify, by number, the location of the bodies of the lumbar vertebrae?

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Slides 58-65 are axial (cross section) MRI’s of the cervical spinal cord (slide 58) through the rostral midbrain (slide 65). All of these sections are T2 weighted. Make note that the orientation of the neuraxis on these radiographic slides is opposite to what you saw on the stained sections (i.e., the dorsal aspect of each scan is toward the bottom of the slide). On slide 58, note the characteristic dorsoventral flattening of the cervical spinal cord and the vertebral arteries located in the foramina transversaria. On slide 59 (caudal medulla), note the vertebral arteries, pyramids and central canal. Slide 60 (rostral medulla) clearly shows the inferior cerebellar peduncles, inferior olive and pyramids as well as the joining of the two vertebral arteries to form the basilar artery. At this level, the central canal has opened up into the 4th ventricle. Slide 61 (transition from rostral medulla to caudal pons) shows the 4th ventricle, middle cerebellar peduncles, CN’s VI, VII & VIII and the basilar artery. Slide 62 (midpons) shows the middle cerebellar peduncle, CN V as it emerges from the middle cerebellar peduncle, 4th ventricle and the basilar artery. Slide 63 (rostral pons) shows the characteristic shape of the ventral pons, as well as the rostral extent of the 4th ventricle, both middle and superior cerebellar peduncles and the basilar artery. Slide 64 (caudal midbrain) shows the characteristic outline of the midbrain, including the cerebral peduncles, interpeduncular fossa and inferior colliculus. At this level, the superior cerebellar arteries can be seen arising from the basilar artery to embrace the midbrain. The internal carotid arteries, uncus and temporal horn of the lateral ventricles can also be seen in this slide. Slide 65 (rostral midbrain) shows a number of structures including cerebral peduncles, interpeduncular fossa, superior colliculi, red nuclei, mammillary bodies, hypothalamus, uncus and third ventricle. In addition, the posterior cerebral, middle cerebral, anterior cerebral and internal carotid arteries can be seen as well as the superior cerebellar cistern. To verify what you are seeing on slide 65, compare it to a similar horizontal wet brain section.

ANIMATIONS

 Coronal MRI  Horizontal MRI

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ASCENDING SENSORY PATHWAYS

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the location and function of each of the described pathways at all levels of the neuraxis, from their origin to their termination in the cerebral cortex. 2. Be able to determine the clinical signs and symptoms resulting from lesions of these pathways at any level of the neuraxis. 3. Trace the two primary ascending sensory pathways from the body and posterior 1/3 of the head and the specific sensory information (modalities) these pathways convey. 4. Demonstrate the somatotopic organization of ascending sensory pathways and how fibers are organized in each pathway. Describe the sensory homunculus of the primary somatosensory cortex. ______

There are a number of ascending pathways in the neuraxis that carry a variety of different types (modalities) of sensory information from the body, extremities and head to the cerebral cortex. Those dealing with the body, extremities and posterior 1/3 of the head receive their input from the dorsal roots of spinal nerves. Those pathways transmitting sensory information to the cortex from the anterior 2/3 of the head (e.g., face, nasal cavities, oral cavity, pharynx, larynx, etc.) receive their input from the cranial nerves. We will concentrate our efforts on those pathways that are clinically relevant and produce consistent, repeatable sensory deficits when lesioned (injured). In studying these pathways, it is best to follow each one from its origins in the spinal cord to its thalamic terminations using the slide set.

Ascending sensory pathways from the body and posterior 1/3 of the head -- The first order (1o) neurons (the first neuron in the pathway) for all sensory pathways from the body and posterior 1/3 of the head reside in the dorsal root ganglia of the spinal nerves. The central processes of these cells enter the spinal cord via the dorsal roots to either synapse in the spinal cord and/or ascend to brainstem levels.

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The nerve fibers in these sensory pathways are typically arranged in a somatotopic (i.e., maintaining an organized relationship to a specific part of the body) fashion throughout their ascent through the spinal cord, brainstem and telencephalon.

1. Anterolateral System (Spinal Lemniscus) a. Lateral spinothalamic tract [Modalities: pain and temperature] b. Anterior (ventral) spinothalamic tract [Modalities: crude (light) touch] c. Spinotectal tract [Modality: pain]. This pathway is the afferent limb of a “reflex” pathway that results in reflexive turning of the head and eyes in response to a painful (nociceptive) stimulus.

These pathways will be studied together since they occupy similar positions within the neuraxis. They are listed above in descending order of their relative clinical importance. The lateral spinothalamic tract is, by far, the most important pathway. The cell bodies of first order neurons for these pathways lie in the dorsal root ganglia in all spinal nerves (except C-1). The central processes of these cells terminate in the dorsal horn in either the substantia gelatinosa or the nucleus proprius. Second order (2o) neurons in these nuclei give rise to axons that cross the midline in the anterior white commissure to assume a peripheral position in the ventral aspect of the contralateral lateral funiculus as the lateral spinothalamic tract (and spinotectal tract), or a slightly more ventral position (anterior spinothalamic tract) (slide 1, slide 2, slide 3, slide 4, and slide 5). As these fibers cross the midline, they ascend 1-3 spinal segments before they join their respective contralateral fiber tracts. How would this bit of knowledge affect the level of sensory deficits if a lesion of the lateral spinothalamic tract occurred at the T-10 spinal level?

These three pathways ascend together throughout the spinal cord and brainstem, and are often referred to collectively as the spinal lemniscus or anterolateral system. When they enter the medulla, they can be found in the lateral aspect just dorsal to the inferior olivary nucleus (slide 9, slide 12, slide 14 and slide 15). In the pons and midbrain (slide 16, slide 17, slide 18, slide 19, slide 20, slide 21, slide 22, slide 23 and slide 24) the spinal lemniscus can be found lateral to the medial lemniscus. The remaining lateral and anterior spinothalamic tracts continue

Neuroscience Laboratory Manual 34 rostrally to terminate in the ipsilateral ventral posterolateral (VPL) nucleus of the thalamus, where third order (3o) neurons in the VPL then project their axons to the postcentral gyrus via the posterior limb of the internal capsule (slide 29, slide 30 and slide 31) and corona radiata.

2. The Dorsal Column / Medial Lemniscus Pathway [Modalities: fine tactile (touch & pressure), vibration, proprioception/kinesthesia (position/movement sense)]

This ascending pathway is anatomically and functionally separated into two distinct pathways within the dorsal columns of the spinal cord. Central processes from dorsal root ganglia (1o neurons) gain access to the spinal cord and ascend in the ipsilateral dorsal column without synapsing in the spinal cord. Information coming into the spinal cord from the lower extremities up to approximately the T-7 spinal level, form a single ipsilateral pathway in the dorsal columns called the fasciculus gracilis (slide 1, slide 2, slide 3 and slide 4). The central processes for dorsal root ganglion cells from T-6 up through C-2 (C-1 spinal nerves have no dorsal root ganglia) ascends in the dorsal columns lateral to the fasciculus gracilis as the fasciculus cuneatus (slide 5 and slide 6). As these pathways ascend into the medulla, they remain in their same relative positions (slide 6). The fasciculus gracilis terminates in the nucleus gracilis, which appears at more caudal levels, while the fasciculus cuneatus continues to ascend to more rostral levels of the medulla to terminate in the nucleus cuneatus (slide 7 and slide 8).

Second order (2o) neurons in the nucleus gracilis and nucleus cuneatus give rise to axons that sweep ventrally as the internal arcuate fibers to cross the midline (sensory decussation/decussation of the medial lemniscus) and form the contralateral ascending fiber bundle called the medial lemniscus (slide 8). These axons then ascend somatotopically within the medial lemniscus through the medulla (slide 9, slide 10, slide 12, slide 13 and slide 14), pons (slide 16, slide 17, slide 18, slide 19 and slide 20) and midbrain (slide 21, slide 22, slide 23, slide 24 and slide 26) to terminate on third order (3o) neurons located in the ipsilateral ventral posterolateral (VPL) nucleus of the thalamus (slide 29).

Third order (3o) neurons in the VPL give rise to axons that gain access to the posterior limb of the internal capsule (slide 29, slide 30 and slide 31). These axons

Neuroscience Laboratory Manual 35 then fan out in the corona radiata to terminate primarily in the postcentral gyrus (Brodmann's areas 3,1,2).

DEMONSTRATIONS

 Posterior Limb of the Internal Capsule

 Postcentral Gyrus (Brodmann’s areas 3,1,2)

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SENSORY PATHWAYS FOR THE ANTERIOR 2/3 OF THE HEAD

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the location and function of each of the described pathways at all levels of the neuraxis, from their origin to their termination in the cerebral cortex. 2. Be able to determine the clinical signs and symptoms resulting from lesions of these pathways at any level of the neuraxis. 3. List the four cranial nerves conveying sensation from the anterior 2/3 of the head. 4. Trace the ascending sensory pathways from the anterior 2/3 of the head and the specific sensory information (modalities) these pathways convey. 5. Discuss how the proprioceptive pathway from the anterior 2/3 of the head differs from pain, temperature, pressure and vibration pathways. 6. Demonstrate the somatotopic organization of ascending sensory pathways and how fibers are organized in each pathway. Describe the sensory homunculus of the primary somatosensory cortex. ______

The vast majority of sensation from the external surface of the anterior 2/3 of the head is provided by the trigeminal nerve (CN V) by way of its three divisions (ophthalmic, maxillary and mandibular) with the remainder being supplied by CN VII, IX and X. With the exception of proprioception and possibly pressure, the 1o neurons in each of the following pathways are located in the sensory ganglia associated with each of the above cranial nerves. For the modalities of pain and temperature, the central processes from each of these sensory ganglia have the same central pathways.

1. Pain and Temperature -- On your whole brain specimens, find CN V and VII, and make careful note of where they emerge from the brainstem. Now observe slide 16 and slide 17. These are cross sections through the caudal pons. On both slides,

Neuroscience Laboratory Manual 37 note the facial colliculus forming the floor of the fourth ventricle, and the fascicles of CN VII as they arch through the pontine tegmentum to exit the brainstem ventrally. Just lateral to the axons of CN VII in the pontine tegmentum is a relatively clear, oval area, the spinal nucleus of V. Surrounding the spinal nucleus of V on the lateral side is a kidney-shaped area of nerve fibers, the descending (spinal) tract of V. Both the spinal tract and nucleus of V are present from this point (i.e., caudal pons) caudally to the level of the upper cervical spinal cord, where they are replaced by Lissaur's tract and the substantia gelatinosa, respectively. Verify this by following the spinal tract and nucleus of V caudally (slide 17, slide 16, slide 15, slide 14, slide 13, slide 12, slide 10, slide 9, slide 8, slide 7, slide 6 and slide 5). 2o neurons in the spinal nucleus of V give rise to axons that cross the midline obliquely and ascend as the ventral trigeminothalamic tract (trigeminal lemniscus). (NOTE: There is still some uncertainty as to the exact location of this tract in humans so we will not require you to know the location of the trigeminal lemniscus in the medulla). As the medial lemniscus flattens dorsoventrally in the pons (slide 16, slide 18, and slide 19), the trigeminal lemniscus remains on its dorsal aspect, sandwiched between the medial lemniscus and the overlying central tegmental tract.

In the midbrain, the trigeminal lemniscus assumes a position along the medial concave surface of the medial lemniscus as the latter fans out laterally and dorsally (slide 20, slide 21, and slide 23) to assume a more vertical orientation. The ascending 2o axons in the trigeminal lemniscus terminate in the ventral posteromedial nucleus (VPM) of the thalamus (slide 29). 3o neurons in the VPM give rise to axons that travel through the posterior limb of the internal capsule (slide 29, slide 30 and slide 31) and through the corona radiata (see demonstration) to terminate in the postcentral gyrus near the Sylvian fissure.

2. Fine Touch, Vibration and Pressure -- The central processes of the trigeminal ganglion cells course into the mid pons via CN V and terminate ipsilaterally on the enlarged rostral extension of the spinal nucleus of V, called the chief (principal) sensory nucleus of V. This nucleus lies in the lateral-most aspect of the pontine tegmentum just medial to the middle cerebellar peduncle (slide 18). The 2o neurons in this nucleus give rise to axons that cross the midline obliquely and ascend to join the trigeminal lemniscus at midbrain levels (slide 20, slide 21, and Neuroscience Laboratory Manual 38 slide 23 ). These nerve fibers then follow the exact synaptic pathway to the cortex as described above for pain and temperature fibers for the anterior 2/3rds of the head. How would the symptoms differ in a lesion of the trigeminal lemniscus in the caudal pons, as opposed to a lesion of this structure at the superior collicular level?

3. Proprioception [and pressure (?)] -- In the case of proprioception, and possibly pressure, the 1o neurons in this pathway do not lie in the trigeminal ganglia, but instead lie within the mesencephalic nucleus of V, which resides in the brainstem from the mid pons to the superior collicular level of the midbrain. In the mid pons, this nucleus is located dorsomedial to the chief sensory nucleus of V (slide 18). The peripheral processes of these cells join CN V to be distributed with the three divisions of this nerve. They accomplish this by forming a small, sickle shaped fascicle of nerve fibers immediately ventrolateral to the mesencephalic nucleus of V. These fibers are called the mesencephalic root (tract) of V (slide 18). In the midbrain (slide 21 and slide 22), the mesencephalic nucleus of V can be seen as a lateral outpocketing of the periaqueductal gray at the approximate level of the floor of the cerebral aqueduct. The mesencephalic root of V can be seen as a thin rim of fibers surrounding the lateral aspect of the nucleus. The central processes of the mesencephalic nucleus of V project to the pontine and midbrain reticular formation (RF), which eventually transmits proprioceptive information to the cerebral cortex, either directly or through the thalamus.

ANIMATIONS

 Somatosensory radiations

DEMONSTRATIONS

 Internal Capsule

 Postcentral Gyrus (Brodmann’s areas 3,1,2)

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THE PYRAMIDAL SYSTEM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the location and function of each of the described pathways at all levels of the neuraxis from their origin in the cerebral cortex to their termination in the brainstem and spinal cord. 2. Determine the clinical signs and symptoms resulting from lesions of these pathways at any level of the neuraxis in which they are located. 3. List which cranial nerve motor nuclei receive unilateral innervation from the corticobulbar tract. 4. Identify the specific brainstem level where the corticospinal tract decussates (crosses) to become the lateral corticospinal tract. 5. Distinguish the major clinical deficits following lesions of upper motor neurons (UMNs) vs. lower motor neurons (LMNs). ______

The term "pyramidal system" refers to the direct, volitional (voluntary) motor pathways from the cerebral cortex to the motor nuclei that control the voluntary muscles of the body, extremities and head. Conversely, the term "extrapyramidal system" (to be studied later) refers to motor pathways from the cerebral cortex that form loops with the basal ganglia and thalamus, and function in more stereotypic movements and maintenance of posture.

Classically, the pyramidal system is subdivided into two parts: 1) the corticobulbar tract, which terminates on cranial nerve motor nuclei within the brainstem and thus controls the voluntary muscles of the head (and some in the neck) and; 2) the corticospinal (pyramidal) tract, which provides descending nerve fibers from the cortex to the motor cell columns in the spinal cord for voluntary movement of the body and extremities.

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Whole and Half Brains; Horizontal and Coronal Sections

Although there are significant contributions from other areas of the cerebral cortex (Brodmann's areas 6,8,1,2,5), both the corticobulbar and corticospinal tracts begin primarily in the precentral gyrus (Brodmann's area 4). Find these regions on your whole and/or half brains. The cortical neurons that reside in the above regions are called upper motor neurons. These upper motor neurons are located somatotopically within the precentral gyrus. The neurons for the corticobulbar tract are located near the Sylvian fissure, whereas the neurons for the corticospinal tract reside somatotopically in the remainder of the precentral gyrus as it arches dorsally and medially. Study the motor homunculus on your lecture handout and make sure you understand this concept. Axons arising from these upper motor neurons descend through the corona radiata, which converges into the relatively compact internal capsule (observe these structures on both your horizontal and coronal sections). The corticobulbar fibers assume a compact position within the genu of the internal capsule, which resides at the rostral pole of the thalamus. The corticospinal axons reside in a compact, somatotopic fashion toward the caudal extent of the posterior limb of the internal capsule. Can you think of a possible negative consequence related to the compact nature of the corticobulbar and corticospinal fibers as they descend through the internal capsule? As we descend from diencephalic to midbrain levels, each internal capsule is continuous inferiorly with the ipsilateral cerebral peduncle. Compare and contrast the appearance and relationship of the internal capsule and cerebral peduncles on the horizontal and coronal slices. This relationship can often be seen particularly well on your coronal slices where the posterior limb of the internal capsule blends inferiorly with the cerebral peduncles. Observing both coronal and horizontal slices, what structure always resides immediately medial to the posterior limb of the internal capsule?

As the corticobulbar and corticospinal axons descend into the midbrain, they are classically described as residing in the middle 3/5 of the cerebral peduncles, with the corticobulbar fibers occupying the medial portion and the corticospinal fibers arranged somatotopically with lower extremity fibers most lateral. The cerebral peduncles can usually be seen cut in cross section on the most inferior horizontal brain slice.

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Look on the ventral surface of your whole brain and note that the cerebral peduncles terminate by disappearing caudally into the convexity of the ventral pons. The pyramidal (corticospinal) tract emerges caudally in the medulla as the pyramids. "What happened to the corticobulbar tract?", you may ask (Try to figure this out before you read on). As the corticobulbar tract descends through the midbrain and pons, nerve fibers from this tract are peeling off to synapse on the motor nuclei of CN III, IV, V, VI and VII. The remaining fibers for the medullary motor nuclei [nucleus ambiguus (motor nucleus for CN IX, X and XI) and the hypoglossal nucleus] have also begun to separate from the corticospinal fibers in the caudal pons to arch dorsally to synapse on these nuclei. Consequently, the vast majority of the nerve fibers in the pyramids are those of the pyramidal (corticospinal) tract. Find the longitudinal median fissure between the pyramids in the rostral medulla. As you follow this distinct fissure caudally, it will blur, or fill in, at the level of the caudal medulla. This is caused by the pyramidal decussation, the crossing of the pyramidal tract to form the lateral corticospinal tract within the spinal cord.

Slide Set (Don't put your brains away yet!)

Now, using your slide set and Fix atlas, follow the respective pathways of the corticospinal and corticobulbar tracts. Begin with slide 35, which is a horizontal section through the diencephalon at the level of the interventricular foramina of Monro. The rostral direction is toward the top of the slide. Identify the anterior limb, genu and posterior limb of the internal capsule. Also note the columns of the fornix, third ventricle and thalamus. Now, find a slice from your horizontally sectioned wet brain specimen that compares to slide 35 and find the same structures as discussed above. Note, on both the slide and the brain slice, the anatomical relationship between the posterior limb of the internal capsule and the thalamus; this relationship serves to identify these structures in a variety of planes.

View slide 32. This is roughly a coronal section through the mid thalamus. Find the thalamus, posterior limb of the internal capsule, third ventricle and massa intermedia. What is the space immediately dorsal to the massa intermedia? As

Neuroscience Laboratory Manual 42 you did previously, find a comparable coronal slice from your wet brain specimens and compare it to this slide while you identify the above structures.

Slide 31, slide 30 and slide 29 show the transition between the posterior limb of the internal capsule and the cerebral peduncles. Identify these structures, as well as the thalamus and third ventricle.

Using slide 24, slide 23, and slide 21, follow and identify the corticospinal and corticobulbar tracts caudally through the midbrain, noting the general location and somatotopic arrangement of these tracts in the cerebral peduncles. On slide 20, slide 19, slide 18, and slide 16, notice how these tracts are separated into loosely arranged fascicles in the ventral pons. The fascicles of the corticobulbar tract are represented in the dorsomedial region of these fascicles.

Slide 14, slide 13, slide 12, slide 10 and slide 9 show the typical, consistent appearance and location of the pyramids from rostral to caudal medulla. Slide 8 illustrates the beginning of the pyramidal (motor) decussation. The median fissure between the pyramids is displaced to the right at its apex and the dorsomedial region of the right pyramid is beginning to move dorsally. The remaining rostrocaudal extent of the pyramidal decussation is illustrated in slide 7 and slide 6, which demonstrate the fibers of the pyramidal tract crossing the midline to assume a more dorsolateral location. Once these fibers attain their new position contralaterally, they are called the lateral corticospinal tract. Slide 5 (spinal cord level C-1) shows the location of the lateral corticospinal tracts as loose fascicles of nerve fibers tucked into the concavity along the lateral surface of the dorsal and ventral horns. The lateral corticospinal tract maintains this position throughout the spinal cord (slide 4, slide 3, slide 2 and slide 1). Would the symptoms be the same in an individual with a lesion of the right pyramid and another individual with a lesion of the right lateral corticospinal tract? Can you explain and coherently defend your answer?

DEMONSTRATIONS

 Cerebral Peduncles  Pyramidal Decussation

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CRANIAL NERVES

Learning Objectives: At the end of the laboratory session students will be able to: 1. Locate and identify the cranial nerves on the wet brains and describe the various functions of each. 2. Describe the types of fibers (i.e., motor, sensory, autonomic, etc.) conveyed by each cranial nerves. Demonstrate a general understanding of “functional components.” 3. Determine the clinical signs and symptoms resulting from lesions involving all components of CN’s I, III, IV, V, VI, VII, IX, X, XI and XII. 4. Review the ascending sensory pathways and pyramidal system laboratories and list which sensory/motor nuclei are associated with specific cranial nerves. ______

There are twelve pairs of cranial nerves. A lesion to any one of these nerves results in clinically demonstrable deficits. As such, any general neurological exam should include an assessment of cranial nerve function. The purpose of this laboratory session is to: 1) (re)acquaint you with the gross anatomy of the cranial nerves; 2) illustrate the internal macroscopic anatomy of selected cranial nerves (CN I, III, IV, V, VI, VII, IX, X, XI and XII); and 3) describe the distinctive functional components (i.e., sensory, motor, autonomic, etc.) found within a given cranial nerve. The remaining cranial nerves (CN II and VIII) will be studied, in detail, in subsequent laboratory sessions.

Whole and Half Brains

Using your whole and half brains, turn them over to view the ventral surface and observe the following:

CN I (olfactory nerve) -- This nerve provides us with our sense of smell. In addition to its unique sensory function, the primary olfactory pathway is also unique among the sensory pathways in that it does not have a relay through the thalamus to the

Neuroscience Laboratory Manual 44 cerebral cortex, but instead sends projections directly to phylogenetically older cortical areas (paleocortex). Another unique aspect of the olfactory pathway is the lack of a decussation (i.e., the pathway is ipsilateral). The 1o cell bodies in this pathway are located in the upper reaches of the nasal cavity. The actual filaments (axons) of CN I extend through the cribriform plate of the ethmoid bone as the olfactory nerves, which project to neurons in the olfactory bulbs.

On the ventral surface of the brain, the olfactory bulbs can be seen on the surface of the frontal lobes near the midline. As the olfactory tract (stalk) extends caudally from the olfactory bulb, it divides into medial and lateral olfactory stria. The medial olfactory stria crosses the midline via the anterior commissure to supply interconnections between the left and right olfactory bulbs. The lateral olfactory stria is the principal central projection pathway for the olfactory system that extends toward the region of the uncus, where it synapses in the primary olfactory cortex (periamygdaloid cortex, piriform cortex) and the amygdala.

CN II (optic nerve) -- The optic nerves mediate vision and are seen in the midline just caudal to the olfactory tracts. The left and right optic nerves meet at the midline and fuse, forming the optic chiasm. Two diverging nerve bundles, the optic tracts, can be seen arching laterally and posteriorly from the optic chiasm to interconnect with the diencephalon and midbrain.

CN III (oculomotor nerve) -- This nerve supplies motor innervation to the extraocular muscles with the exception of the superior oblique and lateral rectus muscles. In addition, it provides preganglionic parasympathetic fibers to the ciliary ganglion, which, in turn, provides postganglionic parasympathetic innervation to the sphincter pupillae muscles and the muscles of the ciliary body that control the shape of the lens. The oculomotor nerve can be seen emerging from the walls of the interpeduncular fossa between the cerebral peduncles of the midbrain. As it emerges, it passes between the posterior cerebral and superior cerebellar arteries before eventually passing into the orbit via the superior orbital fissure.

CN IV (trochlear nerve) -- This small, threadlike nerve supplies motor innervation to the superior oblique muscle of the orbit. If present, it can be seen along the lateral aspect of the cerebral peduncles near their junction with the ventral pons.

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It is the only cranial nerve to emerge from the dorsal aspect of the brainstem. NOTE: Do not attempt to view this nerve on your brain specimens as it emerges from the dorsal midbrain. This can be seen on demonstration. After emerging just caudal to the inferior colliculi, it arches ventrally around the caudal midbrain to dive between the layers of dura mater forming the anterolateral border of the tentorial notch. It gains access to the orbit via the superior orbital fissure.

CN V (trigeminal nerve) -- This nerve supplies sensory innervation to the anterior 2/3 of the head, oral & nasal cavities and soft palate. In addition to supplying motor and proprioceptive innervation to the muscles of mastication, it also supplies motor and proprioceptive innervation to the mylohyoid, anterior belly of digastric, tensor tympani and tensor veli palatini muscles. This large nerve emerges from the rostral border of the middle cerebellar peduncle along the lateral aspect of the pons to enter Meckel's cave, where the trigeminal (semilunar) ganglion resides. Distal to the ganglion, CN V separates into its three divisions (ophthalmic, maxillary and mandibular).

CN VI (abducens nerve) -- This nerve supplies motor innervation to the lateral rectus muscle of the orbit. It can be found near the midline, emerging from the inferior pontine sulcus at the ponto-medullary junction. It courses anteriorly to gain access to the orbit via the superior orbital fissure.

CN VII (facial nerve) -- This complex nerve gives motor innervation to the muscles of facial expression as well as the stapedius, posterior belly of the digastric and stylohyoid muscles. In addition, preganglionic parasympathetic innervation is supplied (via parasympathetic ganglia containing postganglionic neurons) to the lacrimal gland, the submandibular and sublingual salivary glands, as well as the mucous membranes of the hard palate, soft palate and nasal cavities. It also contains sensory nerve fibers that convey taste from the anterior 2/3 of the tongue and general sensation from the external ear. This nerve can be seen as it emerges at the cerebellopontine angle. What foramen does it traverse to gain access to the facial canal?

CN VIII (vestibulocochlear nerve) -- This sensory nerve conducts auditory information from the cochlea and information for equilibrium from the

Neuroscience Laboratory Manual 46 semicircular canals. It emerges lateral to the facial nerve in the cerebellopontine angle and enters the same foramen as the facial nerve.

CN IX (glossopharyngeal nerve) -- This nerve provides motor innervation to the stylopharyngeus muscle. It also contains preganglionic parasympathetic nerve fibers destined for the otic ganglion. Postganglionic fibers from this ganglion are secretomotor to the parotid gland. The sensory nerve fibers in this nerve provide taste and general somatic sensation from the posterior 1/3 of the tongue. It also provides somatic sensation from the pharynx, palatine tonsils, middle ear and visceral information from the carotid body and sinus. This nerve emerges from the postolivary sulcus immediately caudal to CN VIII to pass into the jugular foramen.

CN X (vagus nerve) -- This nerve provides motor innervation to the muscles of the pharynx (except stylopharyngeus), larynx and soft palate (except tensor veli palatini). In addition, it provides preganglionic parasympathetic fibers to parasympathetic ganglia that innervate smooth muscles and glands in the pharynx, larynx and all thoracic and abdominal viscera down to the left colic flexure. It also provides visceral sensory innervation to these same structures as well as taste to the epiglottis and somatic sensory innervation to the external ear and external auditory meatus. This nerve emerges from the postolivary sulcus immediately caudal to CN IX as several compact rootlets arranged in a rostrocaudal fashion and exits the skull via the jugular foramen.

CN XI (spinal accessory nerve) -- This nerve provides motor innervation to the trapezius and sternocleidomastoid muscles. It will not be present on your specimens, since it arises from the lateral aspect of the upper cervical spinal cord to ascend through the foramen magnum and assume a position along the lateral aspect of the medulla before it exits the skull through the jugular foramen.

CN XII (hypoglossal nerve) -- This nerve provides motor innervation to the intrinsic and extrinsic muscles of the tongue. It exits the brainstem as a series of loosely arranged rostrocaudal rootlets arising from the preolivary sulcus. These rootlets converge to exit the skull via the hypoglossal canal.

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Slide Set

CN III (slides 24-22) -- Begin with slide 24. This is a horizontal section through the rostral midbrain. The gray matter that lies dorsomedial to the red nuclei contains the oculomotor nuclear complex. In addition, this nuclear complex contains two small, almond shaped nuclei that lie on its dorsal aspect. These are the Edinger- Westphal nuclei. What specific cell type is contained in the Edinger-Westphal nuclei? Nuclei within the oculomotor nuclear complex gives rise to axons that remain ipsilateral to form CN III on their respective sides. The boomerang shaped white matter immediately lateral to the oculomotor nuclei is the medial longitudinal fasciculus (MLF). This important fiber tract contains axons that interconnect the motor nuclei of CN III, IV and VI. Can you speculate why these nuclei should be interconnected?

On slide 23, find the above structures, including the emerging fibers of CN III along the lateral walls of the interpeduncular fossa. As these fibers emerge from the oculomotor nuclear complex, they fan out laterally and ventrally to pass through the red nucleus before they swerve medially to exit the midbrain ventrally. This phenomenon can be seen clearly on slide 22.

CN IV (slides 21,20) -- On slide 21, the trochlear nucleus replaces the Edinger- Westphal nucleus just ventral to the periaqueductal gray. The small fascicle of axons arising laterally from each nucleus is CN IV as it begins its journey to the dorsal aspect of the pons by arching laterally and dorsally. The medial longitudinal fasciculus can be seen just ventral to the trochlear nuclei and as a thin horizontal strip across the midline. What specific level of the midbrain is represented in this slide?

Slide 20 (rostral pons) is caudal to the trochlear nucleus, a structure of the midbrain. However, it shows the fibers of CN IV in two perspectives: 1) as the axons of CN IV arise from the trochlear nucleus, they turn caudally to form a tight fascicle of fibers in the lateral reaches of the periaqueductal gray, and 2) upon reaching the rostral pons, the fibers of CN IV cross the midline within the superior medullary velum as the decussation of CN IV to emerge from the dorsum of the brainstem as the contralateral CN IV. With this in mind, what clinical symptom(s)

Neuroscience Laboratory Manual 48 would you expect to see following a lesion of the right trochlear nucleus? Also note the medial longitudinal fasciculus along the floor of the periaqueductal gray.

CN V (slide 18) -- Many of the major central components of this nerve have been covered previously under the section entitled "Sensory Pathways for the Anterior 2/3 of the Head" (pp. 38-40). Go back and review that section now, then examine the additional information below.

Slide 18 (middle 1/3 of pons) shows the central sensory and motor structures of V with the exception of the spinal nucleus and tract of V, which reside at more caudal levels. Reacquaint yourselves with the middle cerebellar peduncle, chief sensory nucleus of V, and the mesencephalic tract and nucleus of V. Just medial to the chief sensory nucleus of V is a small fascicle of nerve fibers, the motor root of V. These fibers originated from the clear, egg shaped area, the motor nucleus of V, located just medial to the motor root of V. This motor nucleus supplies the muscles innervated by CN V. Do you remember what they are? Find the MLF on this slide.

CN VI and CN VII (slides 17-16) -- These three slides show the caudal 1/3 of the pons. Slide 17 and slide 16 are essentially at the same level and show many of the same structures. The floor of the fourth ventricle shows a groove at the midline, flanked by gently sloping mounds called the facial colliculi. The clear oval areas immediately subjacent to the facial colliculi are the left and right nuclei of CN VI. Is this a motor or sensory nucleus? Arising from the medial surface of the nucleus of CN VI, and coursing ventrally through the medial lemniscus, are the small fascicles of axons forming CN VI. Just medial to the nucleus of CN VI lie two fasciculi, the more dorsal one is the (internal) genu of CN VII. The other is the MLF. Note the close proximity of the MLF and the nucleus of CN VI. The fascicle of axons arching ventrolaterally from the lateral aspect of the floor of the fourth ventricle is CN VII. Just medial to CN VII in the ventrolateral reaches of the pontine tegmentum is an oval area, the motor nucleus of CN VII. What nucleus and its associated pathway lie just lateral to CN VII in the pontine tegmentum? CN VII can also be seen externally as it emerges just lateral to the ventral pons. A lesion of this nerve would cause what clinical symptom(s)?

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At this point, it is critical to understand the internal path of axons arising from the motor nucleus of CN VII. After arising from the nucleus, these axons travel dorsomedially (cannot be seen here) to pass just caudal to the nucleus of CN VI and lie at the floor of the fourth ventricle near the midline. At this point, they bend rostrally (internal genu of CN VII) to ascend to the rostral pole of the nucleus of CN VI. They then arch over the nucleus of CN VI and proceed ventrally and caudally to exit the brainstem. How does this compare to the internal path of CN IV?

It should also be noted (but not seen) that the superior salivatory nucleus lies on the dorsomedial aspect of each facial nucleus. This important autonomic nucleus supplies preganglionic parasympathetic nerve fibers via CN VII that are secretomotor to the lacrimal gland (via the pterygopalatine ganglion) and to the submandibular and sublingual salivary glands (via the submandibular ganglion).

Slide 13, slide 10 and slide 9 illustrate the location of the nucleus and tractus solitarius. On both sides, the dark “bulls eye” of white matter lying dorsomedial to the spinal nucleus of V is the tractus solitarius, which is encircled by the lightly stained nucleus solitarius. This nucleus and its related tract conduct primarily taste information from CN VII, IX and X. These bilateral structures gradually approach each other to fuse at the midline in the caudal medulla.

CN IX (slides 18-12,10,9) -- Begin with slide 14 (rostral medulla). On the right side, CN IX can be clearly seen emerging from the postolivary sulcus. The pale area immediately dorsomedial to the concavity of the postolivary sulcus contains the nucleus ambiguus. This diffuse motor nucleus resides in the rostral medulla and contributes axons to both CN IX and X. It supplies innervation to the muscles of branchiomeric origin supplied by these two cranial nerves. If you are having difficulty finding this nucleus, do not despair. It lives up to its name in that it is difficult, at best, to pinpoint in any given section. You will have your best luck finding it in slide 12 (light pink ovoid region).

In addition to this motor innervation, CN IX fibers from the inferior salivatory nucleus also supply preganglionic parasympathetic fibers to the otic ganglion for salivary secretions from the parotid gland. This small nucleus lies just medial to the nucleus solitarius (don’t worry about trying to find it).

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Most of the efferent nerve fibers from the nucleus solitarius form the primary ascending taste pathway, which is located primarily in the ipsilateral central tegmental tract. Taste fibers in the central tegmental tract project to the thalamus which, in turn, sends fibers to the postcentral gyrus near the Sylvian fissure (area 43) [gustatory neocortex] and the insula (see demonstration).

CN X (slides 12,10-8) -- Slide 12 shows CN X emerging from the postolivary sulcus on the right side. The vagus nerve contains: 1) the shared contributions from the nucleus ambiguus as previously described [see CN IX above], 2) taste and visceral sensation fibers from visceral structures that use the tractus and nucleus solitarius, and 3) somatic sensation fibers from the region of the external ear that enters the spinal tract of V. In addition, it uniquely contains preganglionic parasympathetic nerves fibers that supply viscera from the head down to the left colic flexure. These axons arise from the dorsal motor (efferent) nucleus of X. The rostral extent of this nucleus can be seen on slide 10; the clear area dorsomedial to the tractus and nucleus solitarius is the dorsal motor nucleus of X. Now follow this nucleus to its caudal extent (slide 9 and slide 8).

CN XI (slides 6,5) -- The motor nerve fibers innervating the trapezius and sternocleidomastoid muscles arise from a special nucleus located in the upper 5 or 6 cervical spinal segments, called the (spinal) accessory nucleus. This nucleus can be seen as a lateral extension of the ventral horn on slide 6 and slide 5. On slide 6, observe the rootlets of the spinal accessory nerve lateral to the spinal cord.

CN XII (slides 10-8) -- This nerve contains motor nerve fibers to the intrinsic and extrinsic muscles of the tongue. They arise from the hypoglossal nucleus, which is located adjacent to the dorsal motor nucleus of X throughout its rostrocaudal extent. On slide 10, locate the dorsal motor nucleus of X. Just ventromedial to this nucleus is a round gray structure, the hypoglossal nucleus. On slide 9, axons can be seen arising from the hypoglossal nucleus and traveling ventrally just lateral to the medial lemniscus to emerge at the preolivary sulcus. Slide 8 shows the caudal extent of the hypoglossal nucleus and a rootlet of CN XII emerging from the preolivary sulcus (both sides).

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NEURORADIOLOGY

Slide 61 is an axial (cross sectional) view of an MRI through the ponto-medullary junction, showing CN VI, as well as CN VII and VIII as they emerge from the brainstem to enter the internal auditory meatus. The cochlea and the semicircular canals can also be seen. Slide 62 is an axial view of an MRI through the midpons, showing CN V as it emerges from the middle cerebellar peduncle and traverses the subarachnoid space to enter into Meckel’s cave.

ANIMATIONS

 Cranial nerves

DEMONSTRATIONS

 Whole brain with cranial nerves  Dorsal view of brainstem showing CN IV  Half brains showing: Insula and Gustatory Neocortex

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NEUROROUND

A 68-year old woman is brought to you by her son. He explains that his mother has lived by herself since the death of her husband 7 years ago. The son is concerned by her “condition” and thinks she can no longer live by herself. He states that she has deteriorated steadily during the last 6-9 months until she can no longer walk, use her right hand to feed herself, or talk clearly, and she has begun to drool. He shares his suspicions with you that she has probably had a series of small strokes and he fears she is becoming senile or demented. Your neurologic exam reveals the following:

1. A right sided hemiparesis with exaggerated deep tendon reflexes 2. A positive Babinski on the right side 3. Anesthesia of the left side of the face up to the vertex of the skull 4. She drools from the right side of her mouth, which droops noticeably, but she can raise both eyebrows. 5. Her speech is slurred. 6. When she opens her mouth to protrude her tongue to say “aah”, her jaw deviates to the left and her tongue deviates to the right.

You order an imaging study of the head and neck region, which shows an external mass compressing one area of the brain.

In your diagnosis of this case, answer the following:

1. Identify the pathways/nuclei or other structures responsible for each deficit/symptom. 2. Given the site of the lesion, are there any other symptoms you may have missed? 3. Given the site of the lesion and its cause, what radiologic technique would give the best results? 4. What types of extramedullary (extra axial) tumors are likely in this region of the brain?

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BASAL GANGLIA

Learning Objectives: At the end of the laboratory session students will be able to: 1. List the main components of the basal ganglia, their location and their general “loop” connections as described in the lab manual and in lecture. 2. Identify the discrete motor deficits (i.e., dyskinesias) and cardinal signs that occur as a result of lesions to different regions of the basal ganglia as described in lecture. ______

The basal ganglia (also known as the "extrapyramidal system") are a group of functionally and anatomically related subcortical nuclei, including virtually all parts of the brain with the exception of the corticobulbar and corticospinal tracts. Because the nomenclature for the basal ganglia can be confusing, the following breakdown or nuclear groupings of the basal ganglia is presented to help alleviate some of the confusion.

1. Corpus striatum

A. caudate nucleus Striatum B. putamen Lenticular Nucleus C. globus pallidus

2. Substantia nigra

3. Subthalamic nucleus

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The connections between 1) the nuclei of the basal ganglia and 2) the basal ganglia and other brain centers are complex and their functional significance is unknown. Consequently, we will condense them into a single, broad based, loop circuit as follows: All areas of the cerebral cortex → via internal & external capsule → striatum (caudate and putamen) and subthalamic nucleus → globus pallidus and substantia nigra → VA, VL and DM nuclei of thalamus → via internal capsule → all areas of cerebral cortex.

Although the basal ganglia per se do not project to the spinal cord, they connect with structures that do (cortex, red nucleus). Through these connections, the basal ganglia function to modulate and integrate somatic motor activity. Through its input from virtually all areas of the cerebral cortex to the striatum and subthalamic nucleus, and its subsequent output from the substantia nigra and globus pallidus to the thalamus and back to the cerebral cortex, the basal ganglia act in concert with the cerebellum as an interface between our sensory and motor systems.

Lesions of the various nuclei of the basal ganglia result in relatively discrete motor deficits collectively called dyskinesias (abnormal involuntary movements). REMINDER: Don’t forget that you should be able to name the discrete motor deficits that arise as a result of lesions to different regions of the basal ganglia as described in lecture.

Horizontal and Coronal Sections

Corpus Striatum (caudate, putamen and globus pallidus) and substantia nigra -- The caudate nucleus forms an incomplete ring around the dorsolateral and ventrolateral aspect of the thalamus and is divided into three parts: head, body and tail. The large head is located rostral to the thalamus, the body along the dorsolateral aspect of the thalamus and the tail curves ventrolaterally to reside in the roof of the inferior horn of the lateral ventricle. The tail terminates at the level of the amygdala. The putamen and globus pallidus reside in the concavity of the caudate nucleus, with the putamen located lateral to the globus pallidus (see Fig. 5 on next page). The substantia nigra is located in the midbrain tegmentum just dorsomedial to the cerebral peduncles. The subthalamic nucleus lies ventral to the thalamus at the junction of the midbrain and diencephalon (this structure will be seen on slides). Neuroscience Laboratory Manual 55

On your coronally sliced brain specimen, select a section just rostral to the anterior commissure. The nuclear mass forming the lateral wall of the frontal horn of the lateral ventricles is the head of the caudate nucleus. Just ventrolateral to the anterior limb of the internal capsule is the putamen. On the next section caudally, the head of the caudate nucleus remains in the same position if the thalamus is not present. However, the putamen is typically joined medially at this level by the globus pallidus. The next section caudally should contain the thalamus. If so, the head of the caudate nucleus has been replaced by the body of the caudate nucleus. If the inferior horn of the lateral ventricle can be seen in the temporal lobe, find the small tail of the caudate nucleus in the roof of the inferior horn of the lateral ventricle. Follow and identify the body and tail of the caudate nucleus, putamen and globus pallidus in subsequent sections. On some of your specimens, the coronal cuts may go far enough caudal that the midbrain has been cut in frontal section. If so, try to find a black-pigmented region in the midbrain tegmentum. This is the substantia nigra. What causes the black pigmentation of this region?

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Select a horizontal section just ventral to the body of the corpus callosum. (NOTE: As you go through your horizontal sections, correlate and compare what you see with the same structures in the coronal sections. This will help you get a better understanding of the three-dimensional anatomy of the basal ganglia). Identify the head and body of the caudate nucleus on this section, if possible. On more ventral sections, identify the head and tail of the caudate nucleus, putamen and globus pallidus. In addition, if the most ventral cut goes through the midbrain, the substantia nigra can be seen as a black-pigmented region just dorsomedial to the cerebral peduncles. If your specimen does not show this, look on your neighbor's specimen and/or look at the demonstrations.

Slide Set

Begin with slide 21. The substantia nigra can be seen at this and all midbrain levels as a pale nuclear region dorsomedial to the cerebral peduncles. Follow the substantia nigra rostrally (slide 22, slide 23, slide 24, slide 25, and slide 28). Lesioning the substantia nigra produces what clinical malady? Note the body and tail (left side) of the caudate nucleus in slide 26, and a close-up of the tail of the caudate nucleus in the roof of the temporal horn of the lateral ventricle on slide 27.

As the transition zone between the midbrain and diencephalon is reached (slide 25, slide 29, slide 30 and slide 31), the subthalamic nuclei appear dorsal to the substantia nigra as fusiform tapered structures resembling cat's eyes. A lesion of the right subthalamic nucleus would produce what SPECIFIC clinical symptom(s)? On slide 31, the globus pallidus can be seen. Some of the dark bundles of fibers running diagonally dorsal to subthalamic nucleus represent output pathways from the globus pallidus and the substantia nigra, that are primarily destined for VL of the thalamus. Also find the putamen and body of the caudate nucleus on this slide and note the relationship between the globus pallidus and internal capsule.

On slide 33 and subsequent slides (slide 34, slide 35 (horizontal), slide 36 (horizontal), and slide 37), identify the caudate nucleus, putamen and the globus pallidus, where possible. Slide 35 shows the fusion of the head of the caudate nucleus and putamen at the rostral extent of the anterior limb of the internal capsule. Neuroscience Laboratory Manual 57

NEURORADIOLOGY

Slide 47 and slide 48 show the head of the caudate nucleus and the putamen. In addition to the above structures, slide 49 also shows the globus pallidus. Slide 50 reveals the substantia nigra (NOTE THE ORIENTATION OF THE MIDBRAIN).

ANIMATIONS

 Caudate nucleus  Striatum  Subthalamic nucleus – Substantia nigra.

DEMONSTRATIONS

 Caudate nucleus  Amygdala

Neuroscience Laboratory Manual 58 NEUROROUND

A family brings in their 67-year old father to the clinic for evaluation. The patient’s daughter notes their concern that “old age seems to be creeping up on Dad rather quickly the last few months.” She goes on to describe how he is slowing down. His wife complains that it often takes forever for him to get dressed and shave in the morning. She states she used to be a nurse and is concerned that he is becoming demented. His son states that when they get out of the car they have to tell him to get out or “he might just sit there forever.” Additionally, he notes a peculiar habit where if his father smiles during a conversation, it just seems to get stuck and stays there well after the topic has moved on. The family is concerned over his state and voices their concern that “Dad may not be ‘all there’.” During all of this, the patient says nothing and moves little.

When you ask the patient to get up out of his chair and follow you into the exam room, he stands up then goes nowhere. He simply stands by the chair. After coaxing him to follow, you begin your physical exam. The exam shows an elderly appearing male appearing a bit older than his stated age. He has a stooped posture. His affect is rather flat and his face expressionless. A very slight tremor of his right hand is noted at rest. Pertinent neurological findings are as follows: 1. CN’s II - XII intact 2. No Babinski or clonus elicited 3. Muscle strength equal bilaterally 4. “Cogwheel rigidity” noted upon flexing and extending each elbow, especially on the patient’s right side. 5. Very slight tremor of the right hand at rest which ceases during finger to nose movements. 6. No significant problems with rapidly alternating movements of the hands; no ataxia in walking; no imbalance with eyes closed; normal finger to nose test. 7. Patient answers questions appropriately. Knows name, date, year, president and knowledgeable of current events.

In your diagnosis of this case, answer the following: 1. What are the three cardinal signs of this patient’s disease? Other manifestations? 2. Discuss the pathways and deficiencies involved. 3. Discuss how pharmaceutical treatment of this disease relates to #2. 4. When symptoms become refractory to medications after long-term treatment, what alternative therapeutic options are available for treatment of this disease? 5. What is the significance of the absence of a Babinski or clonus? 6. What is the significance of the lack of ataxia or problems with finger to nose test or rapidly alternating movements?

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CEREBELLUM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the gross anatomy of the cerebellum and its positional relationship to the cerebrum and brainstem. 2. List the functions of the cerebellum as described in the lab manual and in lecture. 3. Appreciate the functional/clinical consequences of cerebellar lesions. 4. Discuss the blood supply to the cerebellum. ______

The cerebellum (L., little brain) straddles the dorsal aspect of the brainstem. Within the skull, it resides in the posterior cranial fossa immediately inferior to the tentorium cerebelli. It is attached to the brainstem by three paired nerve fiber bundles called cerebellar peduncles. It is through these peduncles that the cerebellum communicates and interacts with other regions of the CNS. By way of these connections, the cerebellum has a profound effect on equilibrium, posture, muscle tone and the coordinated, synergistic muscle contractions required for the meaningful execution of a variety of tasks including walking, speech, eye movements, writing, playing musical instruments, etc. The role of the cerebellum is not to initiate these movements per se, but to insure that these movements, when initiated, are smooth, purposeful and coordinated. NOTE: Voluntary movements (via corticospinal and/or corticobulbar tracts) can be made without cerebellar involvement, but the result is clumsy, disorganized movement (dyssynergia/cerebellar ataxia).

GROSS ANATOMY – Whole and Half Brains

On your whole brains, observe the cerebellum from the dorsal (posterior) side. The superior surface of the cerebellum is flattened and tucked beneath the occipital lobes of the cerebral hemispheres. Gently separate the cerebellum and occipital lobes to view the superior surface of the cerebellum. The midline vermis is

Neuroscience Laboratory Manual 60 elevated on the superior surface with the cerebellar hemispheres gently sloping laterally. Near the middle of the superior surface of the cerebellum is a transverse crease called the primary fissure. It is best seen on demonstration or on your half brains. This fissure divides the cerebellum into anterior and posterior lobes. Do not confuse this fissure with the horizontal fissure, which runs along, or just inferior to, the lip of cerebellum that separates the superior and inferior surfaces. Note the blood vessels ramifying on the superior surface. These are branches of the superior cerebellar arteries and their corresponding veins.

In contrast to the superior surface, the inferior surface of the hemispheres is convex. The midline vermis is depressed and hidden from view, forming the floor of a deep crevice, the posterior median fissure. The falx cerebelli resides in this fissure when the brain is in the skull. Near the midline inferiorly, the cerebellum surrounds the dorsolateral aspect of the medulla with two swellings, the cerebellar tonsils. Occasionally, the cerebellar tonsils are useful in diagnosing elevated intracranial pressure, since they tend to herniate through the foramen magnum as a result of this condition. Two named blood vessels supply the inferior surface of the cerebellum. Their origin and distribution can be highly variable and considerable overlap of territories is not uncommon. The posterior inferior cerebellar arteries typically arise from the vertebral arteries. They arch dorsally around the medulla, giving off small branches to the lateral medullary region, then continue to ramify on the inferior surface of the cerebellum posterior to the tonsils. The anterior inferior cerebellar arteries typically arise from the basilar artery to pass laterally over the cerebellopontine angle and ramify on the inferior surface of the cerebellum anterior to the tonsils. Just lateral to the cerebellopontine angle is a slender lateral projection of cerebellar tissue, the flocculus (part of the flocculonodular lobe). The posterolateral fissure extends laterally from the posterior aspect of the flocculus and separates the flocculonodular lobe from the posterior lobe.

Two of the three cerebellar peduncles can be seen on the ventral surface of your whole brain specimens. The large middle cerebellar peduncle (brachium pontis) lies rostral to the flocculus. Medial to the flocculus, find the inferior olive and postolivary sulcus. The rounded mass dorsal to the postolivary sulcus is the inferior cerebellar peduncle (restiform body). The above two peduncles transmit primarily afferent nerve fibers to the cerebellum. Neuroscience Laboratory Manual 61

Now look at the medial surface of your half brain specimen (see Fig. 6 below). The cut was made through the midline, bisecting the vermis.

The cut midline surface of the cerebellum has the appearance of trees with leaves, called folia, sprouting along the extent of their branches. Like the cerebral cortex, the neurons of the cerebellar cortex lie at the surface in the folia and "branches" of white matter converge in the deeper regions of the cerebellum to form "trunks" that merge to form the deep white matter that constitutes the roof of the fourth ventricle. Imbedded in this deep white matter are the deep cerebellar nuclei (to be seen on slides). The cerebellar cortex at the vermis is separated into nine lobules (identification of some lobules is provided for anatomical reference, not examination purposes). The deep groove between the culmen and declive along the superior surface of the vermis is the primary fissure, which separates the anterior and posterior lobes. Being careful not to tear any tissue, follow this fissure onto the superior surface of the cerebellum. The groove between the nodule (the central part of the flocculonodular lobe) and the uvula along the inferior surface of

Neuroscience Laboratory Manual 62 the vermis is the posterolateral fissure. Note the cerebellar tonsil just inferior and lateral to the uvula.

Now find the superior medullary velum, which forms the roof of the fourth ventricle at its rostral extent. The relatively thick wall of the fourth ventricle at this level is formed by the superior cerebellar peduncle (brachium conjunctivum). This peduncle is the primary pathway for efferents from the cerebellum.

Functional subdivisions of the cerebellum -- Now that you have some knowledge of the gross anatomy of the cerebellum, we can separate it into its functional subdivisions (as described in lecture).

1. Vestibulocerebellum (archicerebellum) -- consists of the flocculonodular lobe a. FUNCTION: EQUILIBRIUM, REGULATION OF EYE MOVEMENT

2. Spinocerebellum (paleocerebellum) -- consists roughly of the vermis and paravermal zones (just lateral to the vermal region), including the tonsil. a. FUNCTION: MUSCLE TONE, STEREOTYPIC MOTOR ACTIVITY (WALKING, STANDING, SWIMMING, ETC.)

3. Pontocerebellum (neocerebellum; cerebrocerebellum) -- consists of the lateral hemispheric zones. a. FUNCTION: MOTOR COORDINATION OF NON-STEREOTYPED (LEARNED, SKILLED) MOVEMENTS

AFFERENT AND EFFERENT CONNECTIONS – Slide Set

There are a number of afferent and efferent pathways for the cerebellum. To list and/or discuss all of them would serve no useful purpose. Instead, we will concentrate on those pathways that can readily be assigned a function that will help in understanding how the cerebellum works through its interconnections with other regions of the CNS.

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Afferent Connections -- The cerebellum receives afferents from the spinal cord and brainstem. These afferents will be studied in an ascending fashion, beginning with the spinal cord.

1. Spinal cord -- In contrast to the dorsal column and spinal lemniscus pathways which transmit conscious information, spinal cord pathways to the cerebellum transmit the unconscious modalities of proprioception, touch and pressure impulses via the inferior cerebellar peduncle to the vermal and paravermal regions of the cerebellum.

2. Brainstem -- Brainstem afferents arise primarily from three sources: A. pontine nuclei; B. vestibular nuclei; C. inferior olivary nuclei.

A. (Cortico)-ponto-cerebellar pathway -- Axons from the cerebral cortex project to the ipsilateral pontine nuclei via the cerebral peduncles. The pontine nuclei then project their axons to the contralateral cerebellar cortex (lateral region of posterior lobe) via the middle cerebellar peduncle.

B. Vestibulocerebellar tract -- From the vestibular nuclei via the juxtarestiform body to the flocculonodular lobe.

C. (Cortico)-olivo-cerebellar pathway -- Axons from the cerebral cortex project to the inferior olivary nucleus (complex). Cells in the inferior olivary complex then project axons contralaterally to all areas of the cerebellar cortex via the inferior cerebellar peduncle.

Begin with slide 19. The cerebral cortex provides axons to the ventral pontine nuclei via the cerebral peduncles. The pontine nuclei within the ventral pons give rise to axons that cross the midline and project via the large middle cerebellar peduncle to the lateral hemispheres of the posterior lobe. Identify the above structures on slide 18, slide 17 and slide 16.

There are four pairs of vestibular nuclei within the medulla and pons. These nuclei provide afferent fibers to the flocculonodular lobe of the cerebellum via the juxtarestiform body (slide 16 and slide 15), which lies in juxtaposition (medial) to

Neuroscience Laboratory Manual 64 the restiform body (inferior cerebellar peduncle). (It should also be noted that this pathway carries efferent fibers from the cerebellum to the vestibular nuclei).

The inferior olivary nucleus projects axons to the cerebellum via the contralateral inferior cerebellar peduncle. Begin with slide 15, which is at the level of the ponto- medullary junction and observe the following: The left and right inferior olivary nuclei each project their axons to the contralateral cerebellar cortex by sending them medially to decussate through the medial lemniscus and continue through the contralateral inferior olivary nucleus to arch dorsolaterally where they enter the contralateral inferior cerebellar peduncle. This can be seen clearly on slide 13 and slide 12.

Efferent Connections -- In contrast to the diffuse origin of afferent connections/pathways to the cerebellum, the vast majority of axons exit the cerebellum via the superior cerebellar peduncle. To understand this concept, consider that the input to the cerebellum comes from a wide variety of structures and travels to all regions of the cerebellar cortex via three peduncles. The output from the cerebellar cortex is also diffuse. However, the vast majority of these cells do not project their axons outside the confines of the cerebellum, but instead send them to converge and synapse on the four pairs of deep cerebellar nuclei, which are located within the white matter in the roof of the fourth ventricle. This relatively compact set of nuclei gives rise to axons that pass primarily through the superior cerebellar peduncle. Because of this compact anatomical arrangement, small lesions to this region (deep cerebellar nuclei, superior cerebellar peduncle) can produce profound effects.

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Deep cerebellar nuclei -- Look at slide 10. The deep cerebellar nuclei are located within the deep white matter of the cerebellum overriding the caudal pons and medulla. They are, from lateral to medial: 1. dentate nucleus -- receives afferents from the Purkinje cells of the lateral hemispheres.

2. emboliform nucleus nucleus interpositus; receives afferents from the Purkinje cells of the paravermal region. 3. globose nucleus

4. fastigial nucleus -- receives afferents from the vermis and flocculonodular lobe.

Now find the above nuclei on slide 11 and slide 14. The fastigial nucleus projects its axons to vestibular nuclei via the juxtarestiform body. Axons from the remaining deep cerebellar nuclei exit the cerebellum via the superior cerebellar peduncle (slide 16 and slide 19). Slide 20 and slide 21 illustrate how the superior cerebellar peduncle arches ventromedially to decussate (decussation of the superior cerebellar peduncle) at the levels of the rostral pons and caudal midbrain. After decussating, these axons pass through the contralateral red nucleus (slide 22, slide 23). Some of these axons terminate in the red nucleus which, in turn, gives rise to axons that decussate immediately and descend to the spinal cord as the rubrospinal tract. This pathway, which provides excitatory motor innervation primarily to the flexor muscles of the upper extremity, can be seen as rounded projections from the ventral surface of the decussation of the superior cerebellar peduncle on slide 21.

Other axons from the deep cerebellar nuclei pass through the red nucleus and ascend to terminate in the ventrolateral (VL) nucleus of the thalamus (slide 31 and slide 32). The VL gives rise to axons that project to the cerebral cortex (Brodmann's areas 4 and 6). This pathway provides information to the cerebral cortex concerning the location of the body in space to ensure smooth coordinated movements.

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Thus, the cerebral cortex forms loop circuits with the cerebellum as follows: cerebral cortex → via int. capsule & cerebral peduncles → pontine & inf. olivary nuclei → via middle & inf. cerebellar peduncles → cerebellum → via sup. cerebellar peduncle → VL of thalamus → via int. capsule → cerebral cortex. Can you recall a pathway or pathways involving the basal ganglia that are similar or have common elements to those of the cerebellum?

Cerebellar Pathology -- There are 4 important concepts to keep in mind when considering lesions of the cerebellum. These concepts are as follows:

1. Lesions of the cerebellum or its afferent or efferent pathways may disrupt normal coordinated movements, but will not cause paralysis. 2. Each cerebellar hemisphere exerts its influence on the muscles of the ipsilateral side of the body. Can you justify this statement anatomically? 3. The flocculonodular lobe influences the axial musculature bilaterally. 4. Lesions of the efferent pathway (deep nuclei and/or superior cerebellar peduncles) produce more profound and permanent deficits than do lesions of the afferent pathways or cerebellar cortex.

NEURORADIOLOGY

On slide 45, find the anterior and posterior lobes, and primary fissure. On slide 46, identify the middle and (decussation of the) superior cerebellar peduncles. Slide 54 and slide 55 show cerebellar pathology. What lobe(s) of the cerebellum is (are) involved? What artery provides the major blood supply to the region of the cerebellar pathology? On slide 60, find the cerebellar tonsils. Slide 61 shows the cerebellar vermis. On slide 62, find CN V emerging from the middle cerebellar peduncle. On slide 63, both the middle and superior (adjacent to 4th ventricle) cerebellar peduncles can be seen.

DEMONSTRATIONS

 Cerebellum -- cerebellar peduncles, cerebellar fissures (primary, horizontal, posterolateral).

Neuroscience Laboratory Manual 67 NEUROROUND

CC: 7 y/o presenting with headache, nausea and vomiting

HPI: This 7 year old is brought to you by his parents who report a 2 week history of worsening morning headaches and occasional vomiting. He had a low grade fever earlier in the week. When seen a few days ago at a local acute care clinic, they were told that he had gastroenteritis. Fluids and suppositories for the vomiting were prescribed. His condition has worsened since then. At times he is somewhat listless. The headaches have not improved and the vomiting is becoming more frequent, now up to 5 times per day. This morning his mom reported his “feeling dizzy” and that he stumbles when he walks.

PE: Acutely ill-appearing 7 year old male. Vital signs normal except for T - 99.5. HEENT: Pupils equally round and reactive to light. Extraocular movements show questionable difficulty abducting each eye. Fundiscopic exam shows papilledema bilaterally. Nose and throat are clear. Chest: Heart normal rate and rhythm with no murmurs. Lungs clear. Abd: No organomegaly, pain to palpation, masses or bruits. Bowels sounds are normal. Neuro: CN’s II - XII intact except for difficulty abducting eyes when to told look laterally. Nystagmus noted on careful examination of the eyes. Gait is ataxic with poor balance. Poor finger to nose test. Rapidly alternating movements of the hands are disordered. Poor check and rebound.

Summary: 7-year old with papilledema and vomiting and neurological changes as noted.

In your diagnosis of this case, answer the following:

1. What is papilledema and what is its significance in a neurological exam? 2. How do the neurological signs help to pinpoint the location of the problem? 3. What signs and symptoms distinguish this patient’s problems as having a neurological basis, rather than gastrointestinal as first thought? 4. What are the diagnostic possibilities? 5. Why the difficulty with abduction of the eyes?

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VESTIBULAR SYSTEM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Identify the vestibular nuclei and relate the functional significance of their connections with extraocular nuclei, cerebellum and spinal cord. 2. Demonstrate how the vestibular system is tested and the normal behavioral consequences of the testing procedures. 3. Discuss the CNs and pathways involved in vestibulo-ocular reflexes. ______

CN VIII (vestibulocochlear nerve) -- As the name implies, the vestibulocochlear nerve has two primary functions: equilibrium (vestibular portion) and hearing (cochlear portion). As such, each division of this nerve has discrete external structures as well as discrete internal nuclei and pathways within the brainstem that serve each of these modalities. In this laboratory session, we will identify the central nuclei and pathways that serve the vestibular division of CN VIII.

Peripherally, hair cells within the ampullae of the semicircular canals, utricle and sacculus are connected with the peripheral processes of the primary vestibular afferents. The cell bodies for these primary afferents are located in the vestibular (Scarpa's) ganglion, which resides in the internal auditory meatus. A few of the central processes of these ganglion cells project directly to the flocculonodular lobe via the juxtarestiform body. However, the vast majority of these central processes project to the ipsilateral vestibular nuclei located in the pons and medulla. The vestibular nuclei give rise to axons that project to spinal cord, cerebellum, extraocular motor nuclei, vestibular nuclei and thalamus. Efferents from the vestibular nuclei to the thalamus are relayed to the postcentral and superior temporal gyri.

Vestibular division of CN VIII -- Beginning with slide 15, locate the inferior cerebellar peduncle. Note: You should know the general location of the vestibular nuclei, however, you do not need to know the specific name and be able to individually identify each one. The "salt and pepper" or speckled region Neuroscience Laboratory Manual 69 dorsomedial to the inferior cerebellar peduncle identifies the inferior (spinal) vestibular nucleus. Medial to the inferior vestibular nucleus lies the medial vestibular nucleus. On subsequent rostral slides, the inferior vestibular nucleus is replaced by the lateral vestibular nucleus. The slender dorsolateral extension of gray matter from the lateral vestibular nucleus is the superior vestibular nucleus. Notice on the left side how the fibers of the juxtarestiform body intermingle with medial and inferior vestibular nuclei. Identify the medial longitudinal fasciculus (MLF) in the midline at the floor of the fourth ventricle. At this level, the MLF contains: 1) ascending axons from the vestibular nuclei to the extraocular motor nuclei (CN III, IV, VI) for coordinating eye movements during the process of maintaining equilibrium and 2) descending bilateral axons from the medial vestibular nuclei for control of somatic muscles in maintaining equilibrium. Identify, where possible, the above structures on slide 13, slide 12 and slide 10.

Using your brain atlas and slide 16, slide 17 and slide 18, follow the MLF and the vestibular nuclei rostrally to get a feel for their location and rostrocaudal extent. As you proceed, also observe the juxtarestiform body on slide 16. How far rostrally would you expect to find the MLF and why?

NEURORADIOLOGY

On slide 61, find CN VII & VIII emerging from the cerebellopontine angle. Also find the internal auditory meatus and the semicircular canals.

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AUDITORY SYSTEM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the anatomy and function of the central and peripheral structures that comprise the auditory system. 2. Compare the differences in symptoms between central and peripheral lesions of the auditory system. ______

Auditory information is transmitted to the CNS via the auditory division of CN VIII (vestibulocochlear nerve). Peripherally, hair cells within the cochlea are in synaptic contact with the peripheral processes of the spiral ganglion cells, which are located in the bony modiolus. The central processes of these cells form the cochlear division of CN VIII.

Observe slide 40. This is a cross section through the cochlea. A brief summary of the spatial organization of the cochlea is provided for reference in locating neural components, although you should be familiar with this information from the corresponding Histology laboratory. The large space at the top of the slide is the scala vestibuli (contains perilymph). The diagonal membrane is called the vestibular (Reissner's) membrane. This structure separates the scala vestibuli and the scala media (cochlear duct). The latter contains endolymph. The cavity at the bottom of the slide is the scala tympani which is continuous with the scala vestibuli at the apex of the cochlea. As such, it contains perilymph. The large structure on the left (modiolus) forms a shelf-like process called the bony spiral lamina. At the tip of the shelf, the basilar membrane stretches to the right to make contact with the spiral ligament which attaches to the outer region of the bony labyrinth (not seen). Resting on the basilar membrane is the (spiral) organ of Corti. Above the basilar membrane at approximately its midpoint, a row of three slender cells can be seen. These are the outer hair cells. Just to the left of these cells is the fusiform space called the space of Nuel. The space just to the left of the space of Nuel is the (inner) tunnel of Corti, which is bounded on the left and right by the inner and outer columns respectively. The inner hair cells reside at the tip of the inner column. In

Neuroscience Laboratory Manual 71 this plane of section, there are typically one row of inner hair cells and 3 rows of outer hair cells. The next space to the left is the internal spiral sulcus. The roof of this sulcus is formed by the translucent tectorial membrane, which extends to the right to make contact with the apical hairs of the inner and outer hair cells. The hair cells are in contact with the peripheral processes of the spiral ganglion cells, which gain access to the hair cells via the bony spiral lamina. The spiral ganglion resides in the modiolus and contains the primary afferent cell bodies in the auditory pathway.

Vibration of the foot of the stapes on the oval window creates displacement of the basilar membrane. This phenomenon produces a shearing effect between the tectorial membrane and the hair cells. When the hairs are displaced because of the shearing forces, the hair cells stimulate the spiral ganglion to transmit impulses into the CNS via the auditory division of CN VIII.

To locate the central auditory pathways, begin with slide 15. On the right side, just lateral to the inferior cerebellar peduncle, there is a large region of mottled gray matter, the ventral cochlear nucleus. Immediately ventral to this nucleus is the darkly stained region of CN VIII as it emerges from the cerebellopontine angle. The clear nuclear area along the dorsal aspect of the inferior cerebellar peduncle is the dorsal cochlear nucleus. Identify, where possible, the above structures on slide 14, slide 13 and slide 12.

Now follow the auditory pathway as it ascends through the brainstem. Beginning with slide 15, note the ventral cochlear nucleus and CN VIII on the right side. The dorsal and ventral cochlear nuclei contain the 2o auditory neurons. Some of the crossed fibers of the ventral cochlear nucleus synapse in the contralateral superior olivary nucleus (SOLN), which can be seen on slide 16. This nucleus is located just lateral to the central tegmental tract and is shaped like an inverted "V". The majority of axons arising from the SOLN enter the ipsilateral lateral lemniscus, which lies just lateral to the SOLN. Find the SOLN, and lateral lemniscus in slide 17. Follow the lateral lemniscus rostrally as it fans out to assume a vertical orientation in the lateral wall of the rostral pons (slide 18, slide 19 and slide 20). On slide 20 (right side), the lateral lemniscus is split into medial and lateral portions by the nucleus of the lateral lemniscus, another relay nucleus in the auditory pathway. On slide 21, the nerve fibers of the lateral lemniscus can be seen sweeping medially Neuroscience Laboratory Manual 72 to innervate the ventrolateral aspect of the nucleus of the inferior colliculus. Axons arising from the nucleus of the inferior colliculus emerge from the dorsolateral aspect of the nucleus to ascend along the lateral wall of the rostral midbrain as the brachium of the inferior colliculus (slide 22). Follow the brachium of the inferior colliculus rostrally as it enters and synapses within the ipsilateral medial geniculate (body) (slide 23, slide 25, and slide 28). Axons arising from the medial geniculate body project to the dorsal aspect of the superior temporal gyrus called the transverse temporal gyrus (of Heschl) (Brodmann's areas 41,42). NOTE: THIS CAN BE SEEN ON DEMONSTRATION.

Given the external and internal anatomy of the auditory system, would a unilateral lesion of the lateral lemniscus in the midbrain produce ipsilateral loss of hearing? If not, what symptom(s) would you expect from this lesion and why? Where would a lesion of the auditory pathway produce total loss of hearing in the left ear?

NEURORADIOLOGY

On slide 61, find CN VII & VIII, the internal auditory meatus and the cochlea.

ANIMATION

 Auditory radiations (transverse temporal gyrus).

DEMONSTRATIONS

 Half brain showing: Auditory cortex (transverse temporal gyrus).

 Dorsal view of brainstem showing: inferior colliculus, brachium of inferior colliculus, medial geniculate.

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VISUAL SYSTEM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Review the functional anatomy of the globe of the eye as learned in Gross Anatomy and Histology. 2. Identify all fiber tracts and cortical structures associated with the visual system. 3. Trace the central visual pathway and describe the consequences of lesions along its course. 4. Describe the pathway of pupillary light reflexes with emphasis on direct vs. consensual light responses. ______

The visual system is a delicately balanced, highly complex system that enables us to see our environment in great detail, and in color. The act of "seeing" or visualizing an object occurs in two phases: The first phase involves light reflecting from an object and passing into the globe of the eye via the cornea. Within the eye, the lens directs and focuses the light onto a specialized region at the back of the eye called the retina. The second stage of visualization is the conversion of this light energy into electrical impulses by the retina. Ganglion cells within the retina give rise to axons that form the optic nerve. Visual information that has been processed by the retina is transmitted through the optic nerve to the optic chiasm where some axons enter the hypothalamus to influence diurnal rhythms. The majority of nerve fibers enter the optic tracts, which project axons to the primary visual cortex in the occipital lobe via a relay in the lateral geniculate body of the thalamus. The primary visual cortex then relays this visual information to other areas of the cerebral cortex for further processing and analysis. Some of the optic tract fibers bypass the lateral geniculate to project into the rostral midbrain where they provide the input for visual reflexes (pupillary dilation and constriction, accommodation and eye movements in response to visual stimuli).

Globe of the eye (slides 41-44) -- We will begin our study of the visual system by examining the globe of the eye. Slide 44 shows a low power view of a horizontal

Neuroscience Laboratory Manual 74 section cut through the equator of the eye. Find the cornea, anterior chamber, iris, lens, posterior chamber, ciliary body and ciliary processes. Now turn to slide 41 and identify these same structures on this higher power view. Also observe the pigmented layer of the iris on this slide. What effect does contraction of the muscles of the ciliary body have on the tension applied to the lens? What effect does this have on the shape of the lens? Would a lesion of the superior cervical sympathetic ganglia have any effect on the shape of the lens? Why (or why not)? Now turn back to slide 44 and identify the vitreous chamber, retina, optic disc, central artery to the retina, optic nerve and dura mater, arachnoid mater and subarachnoid space. Can you explain why the optic nerve is surrounded by meninges? Slide 43 is a high power view of the macula lutea, the region of the retina that produces the best visual acuity, and the posterior wall of the eye. Note the three visible cell layers of the retina, the visual receptor cells (rods and cones), bipolar cells and ganglion cells. The depressed area at the center of the macula lutea is the fovea centralis. What is the unique feature of this region? Also identify the pigment layer of the retina, the choroid layer and the sclera. Between what layers does retinal detachment occur? Why is it important to reattach the retina as soon as possible? Now observe slide 42. This is a high power view of the optic disk and optic nerve. Why is the optic disk called the "blind spot"? Where are the cell bodies of origin for the nerve fibers in the optic nerve? Nerve fibers arising from the nasal (medial) half of the retina cross to the contralateral side of the brain via the optic chiasm. The remaining nerve fibers from the temporal (lateral) half of the retina remain ipsilateral.

The remainder of the visual pathway can be seen on slides 23-26,28,29,31-33 and in the animation. To better understand the plane of section on each of these slides, compare each slide with your half brain specimen. For example, look at slide 33. At the bottom of the slide in the midline is a small part of the infundibulum. Find this structure on your half brain just posterior to the optic chiasm. Approximately in the middle of the slide is the massa intermedia. Find this structure on your half brain. Now draw an imaginary line between the infundibulum and the massa intermedia. This is the plane of section on slide 33. Note the optic tract (slide 33 and slide 32) just lateral to the hypothalamus. Follow the optic tract posteriorly as it diverges to lie just ventral to the cerebral peduncles (slide 31 and slide 29). On slide 28 and slide 26, the optic radiations can be seen emerging from the

Neuroscience Laboratory Manual 75 dorsolateral aspect of the lateral geniculate bodies as they head for the primary visual cortex (area 17). Slide 25 reveals the optic chiasm, and optic tract innervating the lateral geniculate (on left side). The fibers of the brachium of the superior colliculus can be seen after they exit the optic tract to wind around the dorsal aspect of the medial geniculate just ventral to the pulvinar to enter the pretectal area. Some of these fibers cross the midline in the posterior commissure. What is the function of this pathway? The brachium of the superior colliculus, optic tract, lateral geniculate and optic radiations can also be clearly seen on slide 23.

Coronal and Horizontal Sections; Half Brain

Coronal sections -- Starting with the section through (or near) the optic chiasm, follow the optic tracts caudally and attempt to find the lateral geniculate bodies and note the optic radiations emerging from the lateral geniculate bodies.

Horizontal sections -- Select the section that contains the anterior commissure and if possible, find the medial and lateral geniculate bodies. This section should also reveal the optic radiations. It should be noted at this time that axons within the optic radiations that serve the upper visual fields (lower retinal fields) travel rostrally from the lateral geniculate nuclei to loop around the rostral pole of the temporal horn of the lateral ventricles before they turn caudally to join the remaining optic radiations and terminate in the primary visual cortex. Consequently, lesions of the temporal lobe may result in visual field deficits. This indirect pathway is called Meyer’s loop. On the section immediately ventral to this one, try to find the optic tracts as they wind around the brainstem just anterior (ventral) to the cerebral peduncles. NOTE: Whether you see some of these structures will rely on the "luck of the cut". If you are unable to see the above structures on your sectioned brains, look on the brain specimens of one of your neighbors.

Half brain -- On the medial surface, find the parietooccipital sulcus and the calcarine sulcus. The cortex surrounding the dorsal and ventral lips of the calcarine sulcus is the primary visual cortex (area 17), which receives afferents from the lateral geniculate bodies. A good portion of the primary visual cortex is hidden from view, since the calcarine sulcus extends laterally into the occipital cortex. The

Neuroscience Laboratory Manual 76 general cortical region dorsal to the calcarine sulcus is the cuneus. Its counterpart ventral to the calcarine sulcus is the lingula.

NEURORADIOLOGY

Find the optic nerve, optic chiasm, calcarine fissure, cuneus and lingula on slide 45. Can you find the lateral geniculate bodies on slide 46? (Hint: Compare this slide with your coronal brain specimens). The optic radiations can be clearly seen on slide 47, slide 48 and slide 49. A lesion of the optic radiations on the right side would cause what clinical symptom(s)? Could a lesion of the temporal lobes cause visual field deficits? On slide 64, find the optic nerves and globes of the eyes. On slide 65, find the optic tracts.

ANIMATION

 Visual pathway

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DIENCEPHALON

Learning Objectives: At the end of the laboratory session students will be able to: 1. Describe the gross and macroscopic anatomy of the hypothalamus. 2. Define the major functions of the hypothalamus. ______

The hypothalamus is a subdivision of the diencephalon (L., interbrain). Other subdivisions of the diencephalon are listed below:

A. Epithalamus -- consists of habenular nuclei and pineal gland.

B. Subthalamus -- previously studied with the basal ganglia.

C. Thalamus -- the thalamus is, by far, the largest component of the diencephalon. We have studied the various nuclei of the thalamus and its relationship to surrounding structures but will not have a separate laboratory on the thalamus. However, it would serve you well to consider the following: The two thalami lie interposed between 1) the cerebral cortex, 2) basal ganglia, 3) brain stem centers, and 4) spinal cord. Consequently, each thalamus is intimately associated with: 1) the sensory systems, by processing and relaying sensory information to the cerebral cortex, 2) the motor systems, particularly with the motor cortex, cerebellum and basal ganglia and 3) the limbic system, which controls emotion, motivation, learning & memory and sexual behavior. Moreover, the thalamus has reciprocal connections with virtually all areas of the cerebral cortex.

D. HYPOTHALAMUS

Physically, the hypothalamus is a relatively small part of the diencephalon. However, its small size is not an indicator of the importance of this structure. From a functional standpoint, the hypothalamus is a central figure in the regulation of a broad range of bodily functions. Through its endocrine Neuroscience Laboratory Manual 78 connections via the pituitary gland, and its widespread nerve fiber connections with a wide variety of other brain regions and spinal cord, it regulates endocrine, autonomic, emotional and somatic activity.

1. Endocrine system

A. Direct regulation occurs through the hypothalamic-hypophyseal tract (contains axons from the supraoptic and paraventricular nuclei of the hypothalamus) which releases hormones (oxytocin and vasopressin) into the capillaries of the general systemic circulation within the posterior lobe of the pituitary.

B. Indirect regulation occurs through the tuberohypophyseal tract, which delivers "releasing" and "inhibiting" factors to sinusoids in the infundibulum. These factors then gain access to the anterior lobe via the blood vessels of the hypophyseal portal system where they stimulate or inhibit the release of a variety of hormones, such as prolactin, ACTH, LH and others, into the systemic circulation.

2. Autonomic nervous system

A. The hypothalamus is involved in the expression of both parasympathetic and sympathetic functions. Hence, it is often referred to as the "head ganglion of the autonomic nervous system". Consequently, the hypothalamus regulates basic physiologic functions such as temperature regulation, heart rate, blood pressure and gastrointestinal activity. In addition, through its connections with the limbic system, the hypothalamus regulates emotion-based behavior such as anger, rage and sexual activity. To produce these global effects, the hypothalamus has extensive influence via the endocrine system and through synaptic connections within the CNS.

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Whole and Half Brains

On the ventral surface of your whole brain specimens, find the optic nerves (CN II). Gently elevate them and attempt to see the lamina terminalis, which forms both the rostral wall of the 3rd ventricle and the rostral boundary of the hypothalamus. Immediately caudal to the optic chiasm, the infundibulum can be seen. This structure connects the hypothalamus with the pituitary (hypophysis). The region of the hypothalamus between the infundibulum and the mammillary bodies is the tuber cinereum. The rounded swellings of the mammillary bodies form the caudalmost extent of the hypothalamus and reveal the location of the underlying mammillary nuclei.

On the medial surface of your half brain specimens, find the lamina terminalis, optic chiasm, tuber cinereum and mammillary body. The midline region immediately dorsal to the optic chiasm, tuber cinereum and mammillary body is the 3rd ventricle. The wall of the 3rd ventricle from this level dorsally to the hypothalamic sulcus is formed by the hypothalamus. Note how the optic chiasm fuses with the ventral portion of the hypothalamus. It is at this point that axons from the ganglion cells of the retina enter the hypothalamus to provide regulation of diurnal rhythms.

Slide Set

Begin with slide 24 and slide 25, which reveal the mammillary bodies in horizontal sections of the hypothalamus. Slide 29, slide 30 and slide 31 also show the mammillary bodies. Slide 32 is an oblique section in which the hypothalamus is flanked laterally by the optic tracts. The 3rd ventricle can be seen in the midline. Note the hypothalamic sulcus delineating the dorsal extent of the hypothalamus. The large, compact fascicle of axons within the tuberal region is the fornix. This important pathway to the hypothalamus will be discussed as part of the limbic system. Slide 33 is an oblique section through the infundibulum protruding from the ventral surface of the hypothalamus. On slide 33, identify the 3rd ventricle, fornix and optic tracts.

Slide 38 is a relatively high power view of a coronal section through the anterior commissure and rostral extent of the hypothalamus. Unlike all other brain Neuroscience Laboratory Manual 80 sections in your slide set, this region is stained with a cellular stain. As such, the nuclei (cell bodies) will stain darkly with the fiber tracts appearing unstained. Find the 3rd ventricle. The rounded dark areas within the walls of the 3rd ventricle are the paraventricular nuclei. The dorsal aspect of the optic chiasm can be seen as it fuses with the hypothalamus ventrally. The darkly stained region in the lateral concavity between the optic chiasm and the hypothalamus on each side are the supraoptic nuclei. What neurotransmitter(s) is (are) secreted by the cells of the paraventricular and supraoptic nuclei?

NEURORADIOLOGY

On slide 45, the hypothalamus can be seen ventral to the hypothalamic sulcus. The mammillary bodies and infundibulum can also be seen. On slide 65, find the mammillary bodies, hypothalamus and third ventricle.

ANIMATION

 Diencephalon

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THE LIMBIC SYSTEM

Learning Objectives: At the end of the laboratory session students will be able to: 1. Identify the cortical and subcortical structures that make up the limbic system, including salient structures comprising “Papez Circuit.” 2. Relate the anatomical substrates of the limbic system to function. ______

The limbic system is that part of the brain controlling emotion, motivation, learning and memory, and sexual behavior. It is composed of a series of cortical and subcortical structures connected by fiber systems that join these cortical and subcortical structures together to form "closed loop" circuits. Papez Circuit is the most important example of a closed loop circuit and consists of the following connections between limbic structures: hippocampal formation → via fornix → mammillary bodies → via mammillothalamic tract → anterior nuclear group of the thalamus → via anterior limb of internal capsule → cingulate cortex → via cingulum → parahippocampal (entorhinal) cortex → perforant pathway → hippocampal formation. However, many of the structures in this and other loops either receive afferents from other areas of the brain and/or project efferent axons to other structures outside these so called "closed loop" circuits. This enables the limbic system to influence a wide range of behaviors based on a variety of sensory inputs.

In addition to Papez Circuit, other critical structures and pathways in the limbic system include the amygdala, which has connections with the hippocampal formation, hypothalamus, thalamus and septal nuclei.

Half brain; Coronal and Horizontal Sections

Cortical components -- Turn your half brain specimens to observe the medial surface. Immediately rostral to the anterior commissure and lamina terminalis is a small vertical strip of cortex called the paraterminal gyrus. Just rostral to the paraterminal gyrus and immediately ventral to the rostrum of the corpus callosum is the subcallosal gyrus. These two gyri together are often referred to as the septal

Neuroscience Laboratory Manual 82 area. Follow the subcallosal gyrus rostrally to the genu of the corpus callosum where the subcallosal gyrus becomes the cingulate gyrus. The cingulate gyrus extends along the dorsal surface of the corpus callosum from the genu to the splenium. Just caudal to the splenium of the corpus callosum the cingulate gyrus narrows and dives ventrolaterally as the isthmus of the cingulate gyrus. The latter is continuous with the parahippocampal gyrus on the ventromedial surface of the temporal lobe. Due to an involution of the temporal cortex, the hippocampal formation is hidden from view within the depths of the temporal lobe just caudal to the uncus. This region of cortex is best seen on a coronal section.

Select a coronal section immediately caudal to the uncus. Just lateral (deep) to the medial surface of the temporal lobe is an undulating region of cortex buried within the temporal lobe. This is the hippocampal formation. In more caudal coronal sections of the hippocampal formation, this structure has the appearance of a sea horse from which it derives its name (G. hippokampos = sea horse). It is covered ventrally by the parahippocampal gyrus. The region where the medial lip of the parahippocampal gyrus bends 180o to turn dorsally and laterally is called the subiculum, a component part of the hippocampal formation. The paraterminal gyrus, subcallosal gyrus, cingulate gyrus, isthmus of the cingulate gyrus, parahippocampal gyrus and hippocampal formation form a continuous cortical circle or rim called the limbic lobe.

Subcortical nuclear components -- Select a coronal section that includes the uncus. Deep (lateral) to the uncus within the temporal lobe is the rounded subcortical nuclear mass of the amygdala. What sensory pathway has direct connections with the amygdala? Note the close proximity of the amygdala and the hippocampal formation.

Turn again to the medial surface of your half brain specimens. Deep (lateral) to the septal area and immediately rostral to the anterior commissure are the septal nuclei (these will be seen on slides). As previously mentioned, the hypothalamus is a central figure in the limbic system.

Pathways connecting cortical and subcortical components of the limbic system - On the medial surface of the half brain, find the body of the fornix as it arches from caudal to rostral along the ventral border of the septum pellucidum. The fornix is Neuroscience Laboratory Manual 83 the major efferent pathway from the hippocampus. As the fornix approaches the rostral pole of the thalamus, it dives ventrally as the columns of the fornix (see Fig. 7 below).

The majority of axons in the columns of the fornix pass posterior to the anterior commissure and penetrate the hypothalamus where they synapse in the mammillary bodies. Those fibers of the fornix passing rostral to the anterior commissure terminate primarily in the septal nuclei.

As the fornix arises from the hippocampus, it arches caudally and dorsally toward the splenium of the corpus callosum. This can be seen in both horizontal and coronal sections. Select a coronal section immediately caudal to the uncus and a horizontal section looking down on the dorsal aspect of the thalamus just ventral to the body of the corpus callosum. On the coronal section, note the thin strip of white matter that forms the lateral wall of the hippocampal formation. This is the alveus and is formed by the efferent fibers arising from the hippocampus. The alveus courses dorsomedially to form a free lip of white matter called the fimbria, the initial portion of the fornix. Select a more caudal coronal section through the

Neuroscience Laboratory Manual 84 splenium of the corpus callosum (if possible) and observe the fimbriae as they arch dorsomedially to form the crura (sing. = crus) of the fornix.

At this time, try to find the crura, body and columns of the fornix on the horizontal sections. NOTE: If you cannot find the above structures on your sections due to the "luck of the cut", look on your neighbor's specimens and/or look at the demonstrations.

Now follow the body of the fornix rostrally on your coronal sections. Note the relationship between the columns of the fornix and the anterior commissure. In a section containing the anterior thalamic nuclei and/or the mammillary bodies, you may be able to find the columns of the fornix as they dive ventrally within the substance of the hypothalamus to terminate in the mammillary bodies. Find the cingulate gyrus on your coronal sections. The white matter immediately deep to the gray matter of the cingulate cortex is the cingulum, which contains the efferent axons from the cingulate gyrus to the parahippocampal gyrus.

Slide Set

The following slides (26-36,38,39) will reveal cortical regions and subcortical nuclei as well as pathways of the limbic system. As you proceed through these slides, attempt to correlate them with the wet brain specimens.

Begin with slide 26. Immediately dorsal to the pulvinar on both sides lie the crura of the fornix. Sandwiched between the crura is the caudal extent of the body of the corpus callosum. Just lateral to the fornix lies the body of the caudate nucleus. The lower left side of this slide reveals a coronal section through the temporal lobe at the level of the hippocampal formation. The cortical region medially and ventrally is the parahippocampal gyrus.

A higher power view of the hippocampal formation, which is composed of the hippocampus proper, dentate gyrus and subiculum, can be seen on slide 27. The gray matter on the dorsal region of the parahippocampal gyrus where it swerves laterally (i.e., toward left side) is called the subiculum. The hippocampus proper extends from where the subiculum meets the overlying dentate gyrus. The groove between the hippocampus proper and overlying dentate gyrus is called the

Neuroscience Laboratory Manual 85 hippocampal fissure. Note that the hippocampus proper extends laterally from the hippocampal fissure and arches dorsally to terminate by tucking its "head" into the dentate gyrus. The darkly stained white matter dorsal to the dentate gyrus is the fimbria of the fornix, which tapers laterally as the alveus. Identify the choroid plexus extending laterally from the fimbria of the fornix. The space medial to the choroid plexus is the subarachnoid space, whereas the space lateral to the choroid plexus is the inferior (temporal) horn of the lateral ventricle.

Slide 28 is slightly more rostral. Find the fornix, hippocampal formation and inferior horn of the lateral ventricle.

Slide 30 illustrates the origin of the mammillothalamic tract as it arises from the medial aspect of the mammillary nuclei. Where does this fiber tract terminate? Also note the lightly stained uncus of the temporal lobes located ventrolateral to the mammillary bodies. The region deep (lateral) to the uncus is the amygdala.

Slide 31 shows the body and columns of the fornix, mammillothalamic tract, uncus and amygdala.

Slide 32 and slide 33 illustrate the body and columns of the fornix. On slide 33, the mammillothalamic tract is visible on the right side as a looping fascicle of axons approaching the anterior nuclear group from the ventral side.

Slide 36 is a horizontal section through the thalamus. The septal nuclei can be seen just rostral to the columns of the fornix.

Slide 38 is a cellular stain of a coronal section through the anterior commissure. Find the columns of the fornix and the septal nuclei.

Slide 39 is a sagittal section of the brainstem. Is this a midsagittal section? Can you defend your answer based on sound anatomical evidence? Find the body and columns of the fornix, anterior commissure, mammillary body, and mammillothalamic tract.

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NEURORADIOLOGY

On slide 45, find the paraterminal gyrus, cingulate gyrus, and the fornix. What region on this slide represents the septal area? Slide 46 shows the hippocampal formation. Slide 48 and slide 49 illustrate the columns of the fornix.

ANIMATIONS

 Limbic structures (parts, zoom).  Hippocampus, hippocampus-septal nuclei, amygdala-hippocampus.

DEMONSTRATIONS

 Whole brain (ventral view) showing: Hippocampal Formation, Fornix.

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CEREBRAL CORTEX AND REVIEW

Learning Objectives: At the end of the laboratory session students will be able to: 1. Revisit those areas of primary cortex previously learned and review their location and function. 2. Recognize other areas of cortex presented in this lab with particular emphasis on those areas related to speech. 3. List the clinical symptoms related to lesions of cortical areas as presented in lecture. 4. Review and describe the blood supply to all cortical areas. 5. Review and describe the major Brodmann Areas as presented in lecture. 6. Review and describe the sensory and motor homunculi as presented in lecture. ______

The advanced development of the cerebral cortex in humans gives us our unique abilities to participate in language and abstract thinking. The cerebral cortex is also critically involved in our perception of the outside world and our ability to move and adapt to our environment.

Based on phylogenetic relationships and differences in cytoarchitecture, there are three types of cerebral cortex: neocortex, paleocortex and archicortex (i.e., hippocampal formation). Neocortex comprises the vast majority of the cerebral cortex (over 90%) and as the name implies, it is the most recent type of cortex to develop.

Through the years, a number of anatomists have attempted to categorize the cerebral cortex based on neural cytoarchitecture and relate these anatomical differences to the function of specific cortical areas. Overall, Brodmann's (circa 1909) numerical classifications of 52 cortical regions have emerged as the standard and have generally withstood the test of time. However, as more information is gathered on brain function using more sophisticated research techniques, our

Neuroscience Laboratory Manual 88 understanding of the functioning of the various regions of the cerebral cortex, and the CNS as a whole, is rapidly evolving.

To ease your fears, we will only focus on a few of Brodmann's 52 areas of the cerebral cortex that relate to a specific modality or function (Fig. 8). Some of this laboratory session will be a review of cortical areas we have already studied. For example, Brodmann's area 4 of the precentral gyrus contributes axons to the corticospinal and corticobulbar pathways. You should be able to identify the location of these pathways on both your wet brain specimens and your slide sets. You should perform this exercise on all known ascending and descending pathways.

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Whole and Half Brains

On the left lateral surface of the cerebral cortex, identify the central sulcus, precentral gyrus, and the superior, middle and inferior frontal gyri. Make sure you understand the somatotopic arrangement of the precentral gyrus. Identify the general region of the premotor area (area 6) and frontal eye fields (area 8). An ablative lesion of area 8 on the left side results in what symptom(s)? Find the Sylvian fissure. The inferior frontal gyrus lies on the superior bank of this fissure just rostral to the precentral gyrus and is divided into three parts from caudal to rostral. The opercular part of the inferior frontal gyrus is small and lies just rostral to the precentral gyrus; the triangular part resembles an inverted triangle. Both the opercular and triangular portion represent Broca's speech area (areas 44,45). Lesion of this area results in Broca's aphasia. What are the symptoms of Broca's aphasia? What region of the body is controlled by the precentral gyrus immediately caudal to Broca's area? If the Sylvian fissure is gently opened, the insular cortex can be seen. Can you name two sensory modalities that terminate in the insular cortex?

On a lateral view of the left temporal lobe, find the superior, middle and inferior temporal gyri. The dorsal surface of the superior temporal gyrus is hidden by the frontal and parietal opercula, and contains the transverse gyri of Heschl (areas 41,42). What symptom(s) would you expect to observe if Heschl's gyri were lesioned on the left side? The lateral surface of the superior temporal gyrus, approximately from the level of the precentral gyrus rostrally to the posterior portion of the supramarginal gyrus caudally, contains the auditory association area (area 22). The posterior portion of area 22 is Wernicke's area, which acts to integrate visual and auditory information required to comprehend written and spoken language. A lesion of this area results in Wernicke's aphasia. Can you describe the symptoms of Wernicke's aphasia?

Immediately caudal to the supramarginal gyrus of the parietal lobe is the angular gyrus. These two gyri form the inferior parietal lobule. A lesion of the inferior parietal lobule, but not Wernicke's area, results in a complex series of disorders which may include any combination of the following: alexia, anomia, constructional apraxia, agraphia, finger agnosia and confusion or inability to distinguish between the left and right sides of the body. Can you define the above Neuroscience Laboratory Manual 90 terms that describe this lesion? What symptoms would you expect to see in a comparable lesion of the right cerebral hemisphere? What artery supplies this region? Find the postcentral gyrus (areas 3,1,2). This is the somatosensory cortex. What pathways terminate along this somatotopically arranged gyrus?

Find the calcarine fissure at the caudal pole of the occipital lobe. The gyri forming the upper and lower lips of this fissure are the primary visual cortex (area 17). The visual association areas (areas 18 and 19), are arranged concentrically around area 17 on the lateral surface of the occipital lobe. Now follow the calcarine fissure around to the medial surface of the occipital lobe, where this fissure forms a deep horizontal groove that projects laterally. Thus, although area 17 can be seen immediately dorsal (cuneus) and ventral (lingula) to the calcarine fissure, much of area 17 is hidden from view within the depths of the occipital lobe. As on the lateral surface of the occipital lobe, areas 18 and 19 surround area 17. What symptoms would result following a lesion of the left primary visual cortex? What major artery supplies this region? Follow the calcarine fissure rostrally where it is joined by the parietooccipital sulcus. Find the cingulate gyrus, the isthmus of the cingulate gyrus and the paracentral lobule. What Brodmann's areas are encompassed by the paracentral lobule? What part(s) of the body does the paracentral lobule serve? Is the paracentral lobule sensory or motor? What symptoms would you see if it were lesioned? What artery supplies the paracentral lobule? Follow the cingulate gyrus as it curves ventrally around the genu of the corpus callosum to become the subcallosal gyrus. Also identify the paraterminal gyrus. What diencephalic nucleus projects to the cingulate gyrus? To what important system does the cingulate gyrus belong?

Turn to the ventral surface of the brain and identify the uncus and parahippocampal gyrus. What important structure lies deep to the uncus? What clinical symptoms would you see if this structure was lesioned bilaterally? What is the classification of cerebral cortex that comprises the uncus?

The remaining areas of cortex come under the broad heading of association cortices, which correlate the various sensory inputs and deliver them to the appropriate cortical areas for action.

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Intercortical Connections -- Afferent input to the cerebral cortex comes from a variety of subcortical structures. However, the thalamus, via the internal capsule, provides the greatest single source of subcortical input to the cerebral cortex. Similarly, efferents from the cerebral cortex also pass to subcortical structures primarily through the internal capsule. With the possible exception of the visual cortex, virtually all areas of the cerebral cortex interconnect across the midline with comparable cortical areas via subcortical white matter called commissural fibers (pathways). Ipsilateral connections (within the same hemisphere) are accomplished by way of association fibers.

Commissural fibers -- Turn to the medial surface of your half brain sections. Identify the rostrum, genu, body and splenium of the corpus callosum. It is this massive interhemispheric commissure that provides the vast majority of commissural fibers between the cerebral hemispheres. The anterior commissure also transmits interhemispheric fibers between the temporal lobes. Why isn't the posterior commissure included in this group of commissural fibers?

Association fibers -- The general location of association fiber bundles can be determined using a coronal section midway through the body of the corpus callosum. Identify the location of the following fiber bundles within the white matter deep to the cellular layers of the cerebral cortex. The white matter immediately deep (lateral) to the cingulate cortex is the cingulum, which connects the cingulate cortex with the parahippocampal gyrus and hippocampal formation. Just dorsal to the insular cortex lies the superior longitudinal (arcuate) fasciculus, which interconnects ipsilateral frontal, parietal, occipital and temporal lobes. It is the arcuate fasciculus that interconnects Wernicke's and Broca's areas. A lesion of the arcuate fasciculus deep to the parietal operculum produces conduction aphasia. What are the symptoms of conduction aphasia?

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Cerebral Dominance -- In our study of the cerebral hemispheres thus far, they have appeared separate, but equal. That is, there have been similar functions in similar locations in both hemispheres, and each hemisphere primarily controls functions of the contralateral side of the body. However, this concept cannot be applied to the important function of language, which typically resides in one hemisphere only. That hemisphere that controls language is generally agreed to be the dominant hemisphere. In over 90% of humans, the dominant hemisphere is the left hemisphere. The dominant hemisphere is also related to handedness, since 95% of right-handed individuals are left hemisphere dominant. This number drops to approximately 50% in left-handed individuals. It should be noted that a few individuals possess language areas in both hemispheres. It should also be remembered that the non-dominant (usually right) hemisphere should not be viewed as less important, since it is the "dominant" hemisphere when it comes to artistic talent, music and spatial perception.

DEMONSTRATIONS

 Insula, Broca's area, Wernicke's area, Heschl's gyri

 Brodmann's areas

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NEUROROUND

CC: “Mom just isn’t herself any more.”

HPI: Mrs. S. is a 61 y/o homemaker who is brought by her daughter for evaluation. The daughter reports a three-month history of her mother “not being herself.” When pressed to amplify this, she suspects she is depressed, reporting symptoms of apathy, being rather listless and drowsy at times and just not caring about what is going on around her. Her appetite remains good and she sleeps well. She reports this is in stark contrast to her mom’s usual behavior, which has often been described as “the life of the party.” The entire family is concerned about what they perceive as a dramatic change in their mother. The patient reports increasing headaches, worse at night and upon waking. These have occurred for the last six months or so but are generally relieved by taking 800 mg of Ibuprofen four times a day. She has a history of migraine headaches but for which she takes Bellergal tablets and an occasional injection of Imatrex. These medications do not seem to prevent these recent headaches which seem different than her migraines. She also reports occasional dizziness but denies any sensation of the room itself moving. When questioned about what she feels is going on, she simply says her family just can’t cope with the fact that she “getting to be an old woman.” Finally, she reports two or three occasions of nausea and vomiting recently, once with some slight hematemesis. After stepping out of the room so the patient could change for the physical exam, the daughter comes out and tells you that four weeks ago they found her mom incontinent and unconscious on the bathroom floor. She quickly “came to” and after a 20 minute period of being confused, refused to go to the doctor. She said she just slipped and hit her head.

PE: 62 y/o female in no apparent distress, appearing a bit older than stated age: VS: BP 148/100; P - 73 (irregular); R – 15; T - 98.7 HEENT: Extraocular movements intact. Pupils equally round and reactive to light. Funduscopic exam shows papilledema, worse on the right. Nose - clear. Throat: non-erythematous. Neck: Supple with no adenopathy Chest: Lungs clear. Heart rate is normal but “irregularly irregular.” Abd: Non-distended. Mild pain to palpation in the epigastric region. No organomegaly or bruits. Pelvic: s/p hysterectomy with no masses palpated. Rectal exam showed no masses but stool was guaiac positive. MSK: Normal range of motion of limbs. See neuro exam below.

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Neuro Exam: Mood and affect: patient seems rather apathetic; answers questions quite slowly with long pauses between question and her answer,how-ever, her answers are appropriate and more detailed than expected given her general stupor. CN’s II–XII: intact. Muscle strength: 2+ bilaterally except 1+ in left arm (biceps, triceps). DTR’s: (R/L & 2+ is normal) – biceps: 2+/3+ triceps: 2+/3+ knee: 2+/3+ ankle: 1+/3+ Clonus was elicited in the left ankle. Plantar reflexes: down-going on the right; up-going on the left. Gait: slight limp on the left, no ataxia. Other: no dysdiadochokinesia, dysmetria, nystagmus.

LAB: CBC – normal Chest x-ray – mild cardiomegaly, clear lungs. Electrolytes – normal. Barium enema – sigmoid diverticulosis. Upper GI – 2 cm ulcer along the greater curvature of the stomach. MRI of brain – abnormal, results pending.

In your diagnosis of this case, answer the following:

1. What about this patient’s history and physical lead you away from a diagnosis of depression? 2. What do you think had occurred when the patient was found unconscious? 3. What combination of symptoms is ominous? 4. What is the first sign listed in the physical exam that suggests that a tumor might be the cause for this patient’s problems? Assuming this is not a case of metastatic disease, what is the most likely diagnosis and location of the tumor? 5. Which signs suggest an upper motor neuron lesion? 6. What are possible causes for the vomiting? Hematemesis? 7. What does the “irregularly irregular” heart rate suggest and how might it cause neurological symptoms?

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NEUROROUND

A 45 y/o construction worker was hit in the head by a steel beam. Co-workers at the job site ran to his aid and reported that he was unarousable for about 60 seconds then slowly regained consciousness. Over the next 5 minutes or so he was confused about where he was but otherwise could answer appropriately. The EMS was called and transported him to the local Podunk Heights Emergency Room within 15 minutes of his injury.

Upon arrival at the E.R., his vitals signs were normal, including a BP of 133/83. He was alert and oriented time 3, though perhaps slightly confused about why he was at the hospital. Other than reporting a headache, he claimed to feel normal. Physical exam showed a 4 cm scalp laceration over the left temple. Neurological exam showed CN’s II-XII to be intact. There was no muscle weakness. A skull radiograph was reported as normal. His laceration was sutured and he was discharged to home with a prescription for Tylenol #3 as needed for pain.

Three hours later his wife noted that he started to get nauseated and vomited twice. There was no hematemesis. In talking with him, she felt he seemed to be a bit more confused, although he still was able to answer all questions. She decided to take him back to the E.R. for a recheck.

Upon arrival at the E.R., now six hours post-injury, his vital signs were again normal. His pupils were equally round and reactive to light and extraocular movements were intact. No neurological abnormalities were found. He was diagnosed as having a post-concussion syndrome and admitted overnight for observation. Upon arrival at the hospital floor, the nurse checking him in felt he was somewhat lethargic, though arousable. The E.R. physician came up to re- examine him and found some questionable weakness on his right side. A questionable Babinski sign was elicited on the right. Given his questionably changing neurological status, a CT scan of the brain was ordered.

The scan showed a lens-shaped collection of blood beneath the left fronto-temporal region with slight shift of the frontal horns of the lateral ventricles to the right. A neurosurgeon was called. His examination of the patient showed the following: eyes open only in response to pain, left pupil dilated and unresponsive/right pupil minimally dilated and sluggish in response to light, funduscopic exam normal, patient muttering inappropriate words. His breathing became slightly erratic at this point. He also began to show some decorticate posturing and bilateral Babinski signs. His BP found to be 169/82. The patient was intubated and hyper-ventilated. Some IV Mannitol was started then he was taken to the O.R. for an operative procedure.

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In your diagnosis of this case, answer the following:

1. How was this patient’s presentation typical for the problem he has? 2. Discuss the ramifications of the normal skull radiograph, how it helps or hurts making a diagnosis. 3. How do these symptoms differ from a post-concussion syndrome? 4. What is the significance of the right-sided Babinski? Why did it later become bilateral? 5. Explain the changing responses of the pupils reacting to light. 6. Estimate his Glasgow Coma scale rating preoperatively.

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Labeled Atlas of Representative Sections of Spinal Cord and Brain from your Slide Set

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