Brain Scans

FUNDAMENTAL 

NEUROSCIENCE FOR NEUROIMAGING

PART 1: Structural Neuroanatomy of the Human Brain

Introduction

Welcome to fundamental neuroscience for Neuroimaging. 

Since the invention of this methodology, the number of studies using this technique have grown exponentially, from only a few studies reporting on this method in the early 90s to over 16,000 publications using magnetic resonance imaging methods in the year 2014 alone. Studies using MRI initially consisted of only a few data points, with the initial study in 1977 using only 106 individual data points. But this too has grown exponentially with recent studies reporting over 10 billion data points in a single MRI study. 

This scale is even greater when we consider multi-site studies like the Alzheimer's disease neuroimaging initiative, which includes thousands of subjects at multiple sites who each complete multiple visits over time. In that sense, the analysis of modern neuroimaging data is a true big data problem. The goal of the current course is to provide an overview of neuroscience topics relevant to the understanding, analysis, collection and interpretation of neuroimaging data.So what is neuroscience? Neuroscience is the multidisciplinary study of the biological basis of behavior. It includes many disciplines including neuroanatomy (where neuroanatomists focus on delineating the structures of the human brain),  neurochemistry (where chemists look at the chemical properties of communication in the brain), neurophysiology (where people study the electrical properties of the brain) and neuropsychology (where people try to elucidate the cognitive domains and the structures that support those cognitive domains in neuroscience). It also has many different branches of neuroscience including molecular neuroscience, cognitive neuroscience, clinical neuroscience, computational neuroscience, developmental neuroscience, and cultural neuroscience, to name just a few. Neuroimaging is a collection of methods to image the structural, functional and chemical properties of the central nervous system. It is a method that is employed by many disciplines and in many branches of neuroscience. In this course, we will cover a number of course topics to help us understand neuroimaging data, which will include the structural and functional organisation of the brain, terminology of brain organization, brain networks and communication in the brain, cognition and cognitive domains, the principles of magnetic resonance imaging, neuroimaging methods (broadly) and experimental design and neuroimaging studies.

Structure and Anatomy, Part 1

In this module, we'll be discussing the structural anatomy of the human brain. The brain basically consists of two categories of specialized cells. There are the neurons, which are highly specialized and interconnected cellular units of the brain and glia, 

which forms the non-neuronal supportive cellular elements. 

Neurons really form the fundamental processing unit of the brain and in fact the central nervous system broadly. Neurons have many different types, they have many different properties, they have many different shapes and sizes and many different functions. On the top right you can see the complexity of a single neuron. At the bottom, you see different cell types that each have different functions depending on their location on the brain. But most neurons have several basic properties. They have axons, a cell body, dendrites and axon terminals. The axon varies in length and complexity from, in some cases, only a few millimeters long, to quite a distance traveling from one side of the brain to the other side of the brain. It transmits electrical signals from the cell body to the axon terminals towards target neurons. The cell body, contains the nucleus of the cell, which in turns contains DNA. It also contains specialized organelles such as the mitochondria, the golgi apparatus, the ribosomes and polysomes that provide energy and synthesize proteins that facilitate the generation and propagation of the electrical signal along the axon. The dendrites extend from the cell body and they serve as the receiving contact from other neurons. They can branch in very complex patterns as you can see here on the right, in an image from the hippocampus a structure in the brain critical for memory function. It contains dendritic spines which change and form the basis of human learning. The axon terminals are also known as presynaptic terminals. They are very fine branches that form communications sites with other neurons. Most end on the adjoining neuron dendrites but some end on the adjoining neuron cell body. Glia on the other hand, forms the fundamental suppot or scaffolding structure of the brain. Glia form the majority of cells in the central nervous system and they have many different roles.In fact, there are many more glial cells than there are neurons in the brain. They form connective tissue, the structure of the brain, they serve metabolic support roles for neurons, they remove excessive neuronal secretions and they produce myelin, which insulates axons and aids in the electrical propagation of the signal along the axon. Large groups of similar and spatially organized neurons form the basis of the sociable brain structures and networks. We can organize the brain by cytoarchitectural organization, the sociable brain structures and the sociable brain networks. The cytoarchitectural organization of the brain is a structural organization based on cellular composition. It was proposed by the German anatomist Brodmann who published a cytoarchitectural map of the human brain in 1909. 

The Brodmann areas are still commonly used to report the location of neuroimaging findings. On the right, you see an example of a cytoarchitectural map of the human brain showing the different cell types that form organized structures or areas within the brain referred to as Brodmann areas. Brodmann areas are not limited to the human brain. Brodmann also provided Brodmann areas for animals including the hedgehog, the rabbit, the marmoset and the lemur as you can see here. And this provided a comparison method between cell types and cell locations in the animal models comparing them to the human brain organization. We have many desociable brain structures in the brain that can be identified by 

cell type and anatomical boundaries on either an MRI scan or on post-mortem tissues. This has resulted in numerous highly detailed brain atlases available both printed and electronically. On the top right you can see an example of a print of brain atlas with many named brain structures. And on the bottom right, you can see an example of an electronic version of a searchable web page that allowed you to search for brain structures, the location of those brain structures and their proposed function. In addition to brain structures, we have desociable brain networks. Groups of structures in the brain form networks based on their connections between them. The examples are the striatum which includes the nucleus accumbens, the caudate nucleus and the putamen, which are highly interconnected and form a single functional network and the medial temporal lobe which includes the hippocampus, entorhinal and perirhinal cortex which is very important for memory formation. 

In addition to those classifications, there's also a rudimentary anatomical classification based on six lobes. There's the frontal lobe, the parietal lobe, the occipital lobe, the temporal lobe, the limbic lobe and finally the insular cortex. This rudimentary classification is still very valid today because it turns out that those broadly organized structural areas also have common functions associated with them.

Structure and Anatomy, Part 2

[SOUND] In this module, we'll be discussing the vascular anatomy of the human brain. The brain consumes a tremendous amount of energy and oxygen, which is supplied by a highly intricate system of arteries and veins. On the bottom left-hand side, you can see an angiogram of the blood supply to the head and the brain. In the middle, you can see an example of the complexity of the innervation of the blood supply to the brain. And similarly on the right. In the right image, at the top, would be the cortical surface. And as you move down towards the center of the brain, you'll see more and more refined and detail arteries and veins that supply blood to the neurons and glia in that area.The blood is supplied through the internal carotid artery which originates from the aorta. Initially, it forms the common carotid artery which then splits off into the external carotid artery, which supplies blood to the face and skull, and the internal carotid artery, which forms the main blood supply to the brain. From the internal carotid arteries, highlighted with the arrows in this image, blood enters the Circle of Willis. From the Circle of Willis, the blood gets distributed through a series of arteries and veins that each supply blood to specific brain areas. In the middle here, you can see an actual photograph of the Circle of Willis and the arteries and veins entering the bottom of the brain. From the Circle of Willis, blood gets distributed to the anterior cerebral artery, the middle cerebral artery, the posterior cerebral artery, the superior cerebellar artery, the pontine arteries, the anterior inferior cerebellar artery, the vertebral artery, and the posterior inferior cerebellar artery. This highly organized system of blood vessels provides a very specific and organized blood supply to the different areas of the brain. In fact, it is possible to create cortical vascular territories, or areas of the brain, that are supplied in blood from these specific individual arteries. And you will see that these boundaries are fairly specific and there's a little overlap. This is important for neuro-imaging methods methods that we will discuss down the line, that blood is supplied from the specific origin and innervates specific delineated areas of the cortex

Development and Vascular Organization of the Brain

Welcome to this module. In this module, we'll be discussing the developmental and vascular organization of the brain. When we compare our brains across species, we see a great variability in size and shape, between simple animals like a frog all the way up to humans. But when you look at these cross sections of their brains, you also notice a great overlap in basic brain organization. For example, when we look at these MRI images of a human on the left and a monkey on the right, we see great similarities in the basic structures. For example, the cortex pointed out here is, although different in size, very similar between the two. The brainstem including the spinal cord is also very similar. The thalamus which is essentially a relay station important for communication within the brain is very similar, as well as the cerebellum, a structure that is critically important for fine motor control. When we look at these cross-sections of a human on the left and a chimpanzee on the right, we also see great similarities. The corpus callosum which is a bundle of neurons that facilitates communication between the two brain halves, is very similar between these two. As are the hippocampi. The hippocampus is a structure critically important for memory formation and is also very similar in its organization and structure between the animal and the human. Finally, in fact the entire thalamus and midbrain, important for basic life functions, breathing, heart rate but also locomotion and motor control are very similar between this chimpanzee brain and the human brain. But it's even beyond the monkey brains that we can make comparisons. On the left here you see a schematic representation of the brain of a mouse which also has very similar basal structures compared to the human brain. Including the ventricles, the striatum, the thalamus again all structures that are very important for communication in the brain but also locomotion and basic life functions. If you look at the image on the right, you will see that the largest difference between these brains is the size of the cortex. In fact the subcortical brain structures, the basic brain structures of the brainstem etcetera, are very similar between the mouse brain, the cat brain in the middle, and the human brain on the far right. This confirms the great similarities in brain organizations, but again the differences in cortex size across these species. The advantage of these similarities is that it allows experiments in simpler life forms such as the rat or the mouse model that can then be used to inform findings in human neuroscience. The importance of this, the cortex, and also the similarities between the species is also represented in the developmental progress of the brain. On the left you'll see the development of a three week old fetus all the way up to a newborn, and on the right-hand side you can see the development of the neural tube into the spinal cord initially, then the hindbrain which again includes the cerebellum and some of the mid-brain structures. The tectum and the tegmentum which form the midbrain, and finally the endbrain which includes the cortex which is the largest difference between these species. The cortex forms last and represents the largest difference between humans and simpler life forms. So in addition to the developmental anatomy of the brain, we will now discuss a little bit of the vascular anatomy of the human brain. The brain consumes a tremendous amount of energy and oxygen, which is supplied by a highly intricate systems of arteries and veins as you see in these images here. As you see in the right-hand image, the top of the image represents the top of the brain and as you go down further into the brain, deeper into the brain, you'll see the density of the arteries and veins that supply the blood to those regions. Blood is supplied through the internal carotid artery, which originates initially from the aorta. At first this is rough the common carotid artery, which then splits off to the external carotid artery which supplies blood to the face and the rest of the head. And then the internal carotid artery which supplies, which forms the primary blood supply to the brain. So blood is supplied through the internal carotid artery which then terminates into the circle of Willis which distributes the blood throughout the brain. In the middle here, you see an actual photograph of the circle of Willis which is at the bottom of the brain. And on the right-hand side you see a schematic representation of the arteries and veins that come off the circle of Willis. So the middle cerebral artery is the primary blood supply to the circle of Willis, which then distributes the blood through a series of arteries and veins including the anterior cerebral artery, the middle cerebral artery, the posterior cerebral artery, the superior cerebellar artery, the Pontin's arteries, the anterior inferior cerebellar artery, the vertebral artery and finally the posterior inferior cerebellar artery. 

Each of these arteries supplies a very specific and distinct area of the brain with blood. This allows us to create cortical vascular territories or areas of the brain that are supplied by a particular artery or vein system. This becomes important later when we're talking about FMRI research and the origination of the MR signal. So we've discussed a little bit of the developmental and vascular anatomy of the brain to provide an understanding of the basic anatomy. In the next module, we'll discuss some basic terminology that is commonly used to explain locations and relative positions in the brain.

Terminology of Brain Organization

Welcome to this module, in which we will discuss the terminology of brain organization. To describe the locations and physical relationships in the brain, a standard set of nomenclature is often used for vertebrate nervous systems particularly in MRI research. 

In this module, we will step through some of those terms to make you familiar with that language. These terms are commonly used in MRI research to denote relative locations of structures and when we're talking about activations findings or areas of activation in the brain when we're talking about fMRI research. The major axis of the body is called the rostral-caudal axis with the rostral side, the rostrum or beak, representing the front side of the animal and the caudal or cauda tail, the backside of the animal. The second access, the vertical axis of the body is referred to as the dorso-ventral axis. With the dorsal, the back side of the animal and the ventrum refer to as the belly of the animal. So these are four dimensions that are commonly used when we're talking about the anatomy of the animal nervous system. Now in humans, this is a little bit more difficult because we are upright and our brain is tilted, a little bit relative to the animal, we use a slightly different nomenclature to indicate those positions Caudal can still be the back side if we were to apply the terminology used in animals to humans. Dorsal can still be the top of the head, rostral would still be the front side but ventral then would also be the front side if we use that for the belly side of the human. So in humans, we basically need a slightly different set of terms to indicate similar relative positioning. In humans, we use anterior for the front, posterior for the back side, superior for the top side of the brain, and inferior for the bottom side. Medial is referred to as towards the center axis of the body or towards the center axis of the brain, whereas lateral is referred to as moving away from the center axis of the body or brain. In addition to those locations of front and back, and superior and inferior, there are also specific terms for the planes that were going to be studying using fMRI or MRI research. We have the frontal plane, the transverse plane, which is essentially the horizontal plane, and then there's a sagittal plane, which is sometimes also called the sagittal midline which runs from the back of the head essentially through the nose and this plane is referred to as the sagittal plane. When we apply this to MRI images, the planes of orientations are commonly labeled as coronal, which is the same as the frontal plane, axial which is the same as it transverse first plane or sagittal which is again the plane that runs from the nose through the back of the head vertically. These terms allow us to make statements about relative positioning in the brain of either structure or activation findings when we're talking about fMRI. For example, we could say that this sagittal view of the brain shows the cerebellum, which you will see in the white box at the bottom, which is posterior as well as ventral to the frontal cortex. 

Similarly, it allows us to say that the hippocampus in this coronal slice of the brain, is both inferior and lateral to the third ventricles which you see in the white box at the top of the image here. Now, when you notice this image of the coronal plane of the human MRI, note that it is impossible to tell what is the left side of the brain and what is the right side of the brain. You could create this image by standing behind the person but it would look identical if you were to stand in front of the person looking at their brain. So left versus right is a very important issue in MRI studies. As it's impossible to see from the image itself which side is left and which side is right. Again the same image could be generated by looking, standing behind the person or facing the person, looking at the person from the front. So, how's this situation resolved? Well, there are two conventions that are commonly used to address this issue. If the image follows a radiological convention, it means that the left side of the image represents the right side of the person. So the left side of the picture here would represent the right side of the person's face. In counterparts, the neurological convention states that the left side of the image also corresponds with the left side of the person. So in radiological convention, the image would be presented as if you were facing the person, standing in front of the person, whereas the neurological convention essentially it says that you're standing behind the person, looking in the brain and left is left and right is right. In research, both conventions are used and it's usually defined by the analysis software that you're using to process the MRI images. But care must be taken to consistently apply these preferences to accurately report the results. For example, if images are in radiological convention but are mistakenly read as neurological convention, the results of an fMRI study could mistakenly label as findings on either on the left or on the right. To make sure that this is not an issue in reporting results, a lot of studies use what's called a fiduciary marker.This is a magnetic or a metallic object or in some cases a vitamin pill that is placed in the field of view when the image is acquired on the right side of the brain to make sure that on the MRI images it is clearly visible what is the right side and what is the left side of the image. Other commonly used terms in brain organization include proximal, which refers to closer to the point of attachment, distal which refers to further from the point of attachment, ipsilateral which refers to the same side of the brain, contralateral referring to the other side of the brain, and an oblique plane which is a plane that is neither horizontal nor vertical but is at an angle relative to the brain. So we've discussed some basic terminology that is very commonly used in MRI research and MRI data processing. We've now essentially concluded the description of 

the anatomy and the vascular developmental organization as well as terminology. And in the next module, we will move on to discuss how neurons and cells in the brain communicate with each other.

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