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Introduction: This course makes no attempt to teach neuroanatomy in any detail. However, it is useful to be able to understand the descriptive terms that are used to describe the parts of the brain that are the most affected by Alzheimer disease and to know the general location of some of the major structures that are involved. This page seeks specifically to provide simplified answers for some of the questions that about the brain that are likely to arise during a study of Alzheimer disease.

Sources of information: It is somewhat difficult to find books on neuroanatomy that explain these items clearly to a beginner. The best reference I have found is the Atlas of the Human Brain by Mai et al (1997), which is located in the Science Reference area of Norlin Library and does not circulate. I have also cited two other books that do circulate, Ford and Schate (1971), and Nauta and Feirtag (1986). Most of the information on this page has been derived from those sources. The Mai et al Atlas always includes a diagram showing the exact location and orientation of each section that it presents, and the other two books also orient the reader quite well. Another excellent source is the online Whole Brain Atlas, described below.

Additional books: Many other books on neuroanatomy are also available in the QM451 to QM455 range of catalog numbers, both on the Science Reference shelves, and in the circulating part of the Science Library. However, these typically start with a detailed description of the individual types of neurons, of which there are many, with a gradual progression toward larger structures, often organized in terms of the developmental pathways involved in their formation and the primitive embryonic structures that they are derived from. Although this approach is valuable for the student wishing to acquare a complete understanding of neuroanatomy, it is not very helpful to someone who has read about loss of cholinergic innervation to the hippocampus and wants to know where it is and what it looks like.

Overall organization of the brain: The human brain is generally considered to be composed of three major parts, the medulla oblongata , the cerebellum, and the cerebrum. The medula oblongata is essentially the enlarged anterior end of the spinal cord, which is responsible for many basic life sustaining processes, including cardiac and respiratory function, but no higher cognitive functions. The cerebellum has important roles in motor coordination, but is also not involved in higher cognitive processes. Only the cerebrum is of major interest in Alzheimer disease.

Regions of the cerebral cortex: The cerebrum is composed of two nearly hemispherical structures, which are separated by a deep central cleft or sulcus. The cerebral cortex (outer layer) is extensively folded and separated into a number of bulging structures known as gyri (singular = gyrus) by deep clefts known as sulci (singular = sulcus). The cerebral cortex is often described in terms of four geographical areas, each with left and right halves.

• The frontal cortex is the area at the front of the brain.
• The temporal cortex is at the side, corresponding more or less to the area between the eyes and the ears.
• The parietal cortex is at the top and upper back of the brain.
• The occipital cortex is at the lower back of the brain, extending somewhat over the cerebellum and medula oblongata.

Subcortical areas: Structures located in the limbic region, deeper into the brain, that are also of importance in the study of Alzheimer disease include the amygdala and the hippocampus. These regions can perhaps best be viewed as the extreme lateral edges of the cerebral cortex that have have been folded under the main structure and lie on either side of the ventricles (hollow cavities) that extend from the spinal column upward and forward through the brain. The amygdala and hippocampus are usually shown in coronal sections (explained below), to illustrate their location relative to the rest of the cortex. However, such views fail to emphasize the front to back length of these relatively elongated structures.

Basal forebrain: The final area of special interest to this class is a region at the lowest level of the forebrain, known as the substantia innominata, which contains three centers of cholinergic innervation that project long axons to all of the regions of the brain that suffer from loss of cholinergic innervation in alzheimer's disease (cortex, amygdala, hippocampus).

Terminology used to describe sectional views of the brain: Because the brain has extensive internal structure, as well as a highly convuluted surface, it is necessary to employ cross-sectional views to visualize its internal structure. Classically, these have been large-scale histological sections, but modern methods of magnetic resonance imaging (MRI) and computed X-ray tomography (CAT scan) have made it possible to obtain quite detailed serial sectional views from living individuals by non-invasive means. Unexpectedly, I have encountered a lack of consistency in the way serial sections through the human brain are named. This probably derives at least in part from the upright posture of humans relative to other mammals, which also confuses other body coordinates, such as what is meant by anterior (the front part of the individual). The nomenclature used here is from Mai et al. (1997). In some cases the nomenclature used by Nauta and Feirtag (1986) is different.

• A coronal section cuts along the long axis of the body from left to right, thus separating ventral (anterior in humans) from dorsal (posterior in humans). A coronal section of the cerebrum shows left and right halves of the cerebral cortex, with a deep cleft between them, as well as the various structures that join the halves together and provide communication bettween them. For reasons that are not yet clear to me, these sections are referred to as frontal sections by Nauta and Feirtag (1986). Their book contains good "frontal" sections that show structures of special interest to the study of Alzheimer disease. The left and right amygdala can be seen in Figures 99 and 100, and the hippocampus in Figure 101. The substantia innominata is shown in Figure 98 (This is the area that contains the nuclealis basalis of Meynert and related centers of cholinergic innervation, which are not identified in the figures, but which are discussed on pages 242-243. The Mai et al (1997) atlas also contains a very clearly labeled series of coronal sections.

• A hortizontal section is one that is cut across the long axis of the body. Horizontal sections can be viewed as a series of thin slices through the brain starting at the top of the head and working downward. However, conventional numbering of sections normally starts at the base of the brain and works upward to the top of the head. An excellend series of horizontal sections derived from magnetic resonance imaging is available through the online whole brain atlas, whose use is described below , including instructions for locating some of the structures described above. The Mai et al. (1997) atlas also contains an extended series of well labeled hortizontal sections.

• A sagittal section is one that is parallel to the midline of the body and separates left from right. Most textbook sagittal sections are cut at the midline of the brain. However, to see structures such as the amygdala and hippocampus that are positioned somewhat laterally and do not extend to the midline, it is necessary to view a saggital section that is cut somewhat off center (for example, figure 77 in Ford and Schade, 1971).

The whole brain atlas is an online collection of MRI and CT images of normal and diseased brains.

• Probably the best place to start to click on the Atlas of Normal Structure and Blood Flow. This will bring up a series of coronal sections . The first one presented is at the level of the eyes (section 24). You can move up or down one section by clicking on the arrows, or you can go to any desired level by clicking on the small sagittal section that shows the level of the coronal sections. Labels identify structures of interest in the various sections. The amygdala is identified in section 23, and the hippocampus in section 21. There is also a movie that allows you to zoom up and down (but without labels). If you use it, you will need to slow the movie player down to about 1 frame per second, or else set it to advance the frames manually.

• You also have the option of several different views of the same section. The default is the MRI T2 setting. This gives the best overall view of the tissue. However, if you want to see where the cavities are in the brain, particularly with regard to the hippocampus and amygdala, try the T1 setting.

• There is also a list of the top 100 brain structures that you can click on and be taken to the sections that identify the particular structures that you are interested in.

• After you become somewhat familiar withthe operation of the system and overall brain structure, you can scroll down the home page and obtain images of Alzheimer disease brains, including a guided tour that points out special features in each section. There are also hyperlinks that take you to sections that identify some of the structures that are discussed in the text.

References:

Ford, D.H.; Schade, J.P. 1971. Atlas of the Human Brain. Elsevier, amsterdam. (Norlin QM455 F62 1971). Figure 77 is a sagittal section showing both the amygdala and the hipocampus. It provides a better overall view of the extent of these structures than the usual frontal or coronal views. Figure 70 shows the hippocampus in a frontal section. A variety of other cross-sectional, exterior, and partially dissected views of the brain are also provided.

Mai, J.K.; Assheuer, J.; Paxinos, G. 1997. Atlas of the Human Brain. Academic Press, San Diego. (Science Reference, noncirculating, QM455 M347 1997). This atlas has large well labelled sections of the human brain in various planes. It is particularly easy to use because every page includes a diagram that orients the reader to the exact location and plane of the section. There is also a very detailed index of brain structures that lists every page on which any given structure is identified. Although it can only be used in the library, this is the best resource that I have found for identificaiton of specific brain structures.

Nauta, W.J.H.; Feirtag, M. 1986. Fundamental Neuroanatomy. W. H. Freeman & Co., New York. (Norlin QM451 N38 1986). This book contains a series of "frontal" (coronal) sections (figures 95-103) that illustrate the basal and limbic structures of interest to this course, including the substantia innominata (figure 98), amygdala (figures 99 and 100), and hippocampus (figure 101). Each figure presents both a photograph of a stained section and an interpretive drawing. Note that the Wiegert stain causes the white matter (myelinated axons) of the brain to appear black, and the gray matter (non-myelinated areas) to appear yellow.

Wurtman, R. J. 1985. Alzheimer'sDisease. Scientific American 252(1)62-74 (January). This article, which was distributed in class, provides an introductory explanation of the cholinergic theory of Alzheimer disease, including a figure on page 73 depicting the major cholinergic pathways .