Tag: neuroanatomy

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Claustrum of the Brain

The claustrum is a thin, irregular sheet of neurons situated between the insular cortex and the striatum within each cerebral hemisphere of the brain. Despite its small size and somewhat elusive nature, the claustrum is believed to play a significant role in various cognitive processes. Here’s a detailed look at its structure, connections, and proposed functions:

Structure and Location

  • Location: The claustrum is located deep within the brain, nestled between the insula and the putamen of the basal ganglia. It is part of the telencephalon.
  • Anatomy: It is a slender, elongated structure composed of a dense network of neurons and fibers. The claustrum has two distinct parts: the dorsal and ventral claustrum.

Connections

  • Cortical Connections: The claustrum has extensive bidirectional connections with almost all areas of the cerebral cortex. These connections are topographically organized, meaning that different regions of the claustrum connect to specific cortical areas.
  • Subcortical Connections: Besides its cortical connections, the claustrum also interacts with subcortical structures, including parts of the thalamus and basal ganglia.

Proposed Functions

  1. Integration of Sensory Information:
    • Multisensory Processing: One of the primary hypotheses is that the claustrum acts as a hub for integrating multisensory information. It receives inputs from various sensory modalities and may help in creating a unified perceptual experience. This integration is thought to be critical for coherent perception and consciousness.
  2. Attention and Consciousness:
    • Attention Modulation: The claustrum is believed to play a role in controlling attention. It might help focus attention by selectively enhancing relevant sensory inputs and suppressing irrelevant ones. This function is crucial for maintaining a cohesive stream of consciousness.
    • Consciousness: Some researchers have proposed that the claustrum could be involved in generating or maintaining consciousness. This idea stems from its widespread cortical connections and its potential role in integrating information across different brain regions.
  3. Coordination of Cortical Activity:
    • Synchronization: The claustrum may help synchronize activity across different cortical areas, facilitating coordinated neural activity necessary for complex cognitive tasks. This synchronization could be essential for tasks that require the integration of information across different domains, such as language processing and spatial awareness.
  4. Cognitive and Behavioral Functions:
    • Learning and Memory: Although less understood, the claustrum might have a role in learning and memory processes. Its connections with the hippocampus and prefrontal cortex suggest potential involvement in these functions.
    • Executive Function: The claustrum’s interaction with the prefrontal cortex indicates it could be involved in higher-order executive functions, such as decision-making, planning, and inhibitory control.

Research and Clinical Implications

  • Lesion Studies: Studies involving lesions or dysfunction in the claustrum have provided insights into its potential roles. Damage to the claustrum has been associated with disruptions in attention, sensory processing, and consciousness, supporting its proposed functions.
  • Epilepsy: The claustrum has been implicated in certain types of epilepsy, where abnormal activity in this region might contribute to the spread of seizures across the cortex.
  • Neurological and Psychiatric Disorders: Dysfunctions in claustral activity or connectivity might be related to various neurological and psychiatric conditions, such as schizophrenia, autism, and Alzheimer’s disease. Understanding its role could lead to new therapeutic approaches.
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Blood-Brain Barrier

The blood-brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). It plays a critical role in maintaining the homeostasis of the CNS, protecting it from potentially harmful substances, and regulating the transport of essential molecules.

Structure of the Blood-Brain Barrier

  1. Endothelial Cells: The primary component of the BBB is the endothelial cells that line the capillaries in the brain. Unlike endothelial cells in other parts of the body, those in the brain are tightly joined together by complex structures called tight junctions. These tight junctions prevent most substances from passing between the cells, forcing materials to pass through the cells instead.
  2. Basement Membrane: Surrounding the endothelial cells is a thin, fibrous extracellular matrix called the basement membrane. This layer provides structural support and further regulates the movement of substances.
  3. Astrocytic End-feet: Astrocytes, a type of glial cell, extend their end-feet processes to cover the surface of the capillaries. These end-feet secrete factors that maintain the tight junctions and overall integrity of the BBB.
  4. Pericytes: These contractile cells are embedded in the basement membrane and play a role in regulating blood flow, maintaining the BBB, and participating in immune responses within the CNS.

Function of the Blood-Brain Barrier

  1. Selective Permeability: The BBB selectively allows the passage of essential nutrients, such as glucose and amino acids, while restricting the entry of harmful substances, pathogens, and large molecules. Transport proteins facilitate the movement of these nutrients across the endothelial cells.
  2. Protection: By restricting the entry of potentially neurotoxic substances and pathogens, the BBB protects the brain from infections and toxins that could disrupt neural function.
  3. Homeostasis: The BBB helps maintain the ionic balance and extracellular environment of the CNS, which is crucial for proper neuronal function. It regulates the levels of ions, neurotransmitters, and other substances in the brain.
  4. Metabolic Barrier: Enzymes within the endothelial cells metabolize certain substances, providing an additional layer of protection by breaking down potentially harmful compounds before they can reach the brain tissue.
  5. Immune Surveillance: While the BBB limits the entry of immune cells, it is not completely impermeable to them. Microglia, the resident immune cells of the CNS, and pericytes play roles in immune responses, providing a controlled environment for immune surveillance and response.

Transport Mechanisms

  1. Passive Diffusion: Small, lipophilic (fat-soluble) molecules can diffuse passively across the BBB. Examples include oxygen, carbon dioxide, and certain lipid-soluble drugs.
  2. Facilitated Transport: Specific transport proteins and carriers in the endothelial cell membranes facilitate the movement of essential hydrophilic (water-soluble) substances like glucose and amino acids. An example is the GLUT1 transporter for glucose.
  3. Active Transport: Certain substances require active transport mechanisms, which use energy (ATP) to move molecules against their concentration gradient. This is seen with ions and other essential molecules.
  4. Receptor-Mediated Endocytosis: This mechanism involves the binding of specific molecules to receptors on the endothelial cell surface, triggering endocytosis and transport into the brain. Examples include insulin and transferrin.

Challenges and Clinical Implications

The BBB poses a significant challenge for drug delivery to the brain, necessitating the development of novel strategies to treat CNS disorders. Conditions such as multiple sclerosis, Alzheimer’s disease, and stroke can disrupt the BBB, leading to increased permeability and subsequent neural damage. Understanding the BBB’s function and structure is crucial for developing therapeutic interventions that can protect or restore its integrity in these diseases.

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Introduction to the Human Brain

The human brain is an incredibly complex and intricate organ, consisting of approximately 100 billion nerve cells (neurons) and trillions of supportive glial cells. It is the central control center for the body and is responsible for coordinating and integrating all bodily functions, from basic reflexes and movement to higher cognitive processes such as learning, memory, and decision making.

The brain is divided into three main divisions: the cerebrum, the cerebellum, and the brainstem. The cerebrum is the largest and most complex part of the brain and is responsible for most higher brain functions. It is divided into two hemispheres (left and right), which are connected by a bundle of nerve fibers called the corpus callosum. The cerebrum is further divided into four main lobes: the frontal lobe, parietal lobe, temporal lobe, and occipital lobe.

The frontal lobe is located at the front of the brain and is responsible for a variety of functions including voluntary movement, problem solving, planning, and decision making. The parietal lobe is located behind the frontal lobe and is responsible, among other functions, for processing sensory information from the body, such as touch and temperature. The temporal lobe is located on the sides of the brain and is responsible for processing auditory information and memory. The occipital lobe is located at the back of the brain and is responsible for processing visual information.

The cerebellum is located underneath the cerebrum and is responsible for coordinating voluntary movement and balance. It also connects to the frontal lobes and other brain regions and is involved in most functions. The brainstem is located between the cerebrum and the spinal cord and is responsible for controlling many of the body’s basic survival functions such as heart rate, blood pressure, and breathing.

The brain is surrounded and protected by the skull, which is made up of 22 bones that are fused together. The brain is also surrounded by three layers of protective membranes called meninges. The outermost layer is the dura mater, the middle layer is the arachnoid mater, and the innermost layer is the pia mater.

The brain is supplied with blood by two main arteries: the carotid arteries and the vertebral artery. These arteries branch off into smaller arteries that supply the various regions of the brain with blood.

The brain receives a constant supply of oxygen and nutrients from the blood and removes waste products through a network of tiny blood vessels called capillaries. The brain also has its own system of waste removal called the glymphatic system, which helps to remove waste products such as amyloid beta, a protein that has been linked to the development of Alzheimer’s disease.

One of the most important cell types in the brain are neurons, which are responsible for transmitting information throughout the brain and body. Each neuron has a cell body, dendrites, and an axon. The cell body contains the cell’s nucleus and other organelles, and the dendrites receive signals from other neurons. The axon is a long, thin extension of the cell body that sends signals to other neurons or muscles.

Neurons communicate with each other through a process called neurotransmission. When a neuron receives a signal, it sends an electrical impulse down the axon to the terminal buttons, which release chemical neurotransmitters into the synapse (the small gap between neurons). These neurotransmitters bind to receptors on the dendrites of the receiving neuron, transmitting the signal across the synapse.

In addition to neurons, the brain also contains a variety of other cell types, including glial cells. Glial cells, also known as glia, are non-neuronal cells that provide support and insulation for neurons. There are several types of glial cells, including astrocytes (astroglia), microglia, and oligodendrocytes. There is a growing interest in the functions of glial cells, including their role in neuroinflammation, metabolism, and other functions.

In summary, the brain is complex. It allows us to have life as well as learn from and experience the world around us.

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Modems and White Matter

Yesterday my connection to the Internet decided to stop working. I tried restarting the cable modem, the wireless router, and other attached devices. That didn’t fix the problem. That’s usually a good first step though. I saw that the internet connectivity light was lit on the modem but the PC/Activity light was not lit. That told me that maybe the router was bad. I tried plugging my computer directly into the modem via ethernet and my computer did not recognize that a cable was plugged in. I had discovered what was wrong. While it hadn’t taken me long to figure out the problem, I did what many people do and look for solutions in the hardware first rather than in the connections. That’s not necessarily wrong, cables are more hardy than electronic components, but it did reveal my biases. So what was the problem?

The components were all okay – modem, router – but the connections were not. Wiring was the problem. Being interested in the brain, I immediately knew this would make  great brain analogy.

When someone’s cognitive functioning changes, one of the first things clinicians usually jump to is which part of the cortical or subcortical gray matter went bad, so to speak. While those components can and do go bad, we often overlook, just as I did at first, the connections. In my case, the ethernet cable had gone bad. There are many times when what’s affected in the brain are not the components but rather, the wiring – the axons. White matter might be just as important or even more important than the gray matter for cognition, even if its contribution might be more subtle. Much of my current research revolves around this idea.

So the moral of the story is that when things are not working correctly, the wiring might be the culprit.

How did my ethernet cable get damaged? Maybe it just stopped working spontaneously but it also had experienced a bit of acute stress earlier in the day (the modem fell off its stand). Something might have happened to the cable during this time. The white matter of our brain can similarly be affected by traumatic injury, nontraumatic injury (anoxia, hypoxia, etc.), stroke, or a long history of cerebrovascular problems. Just as we can take care of our electronic equipment (by not dropping it or knocking it off its home or stepping on it or whatever else we can do to our technology), we can take care of our white matter by avoiding similar injuries.

Exercise, weight control, managing diabetes, managing blood pressure, and managing cholesterol, can all help protect white matter from going bad and disconnecting different brain areas. We can’t connect to the Internet if our wiring is bad.

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Video Introduction to the Cingulum

I posted this on my neuroimaging blog and thought I should post it here too. This is a video I put together about the cingulum, a prominent white matter fiber track in the brain that is involved in emotion, attention, memory, among many other functions. All images except one from Gray’s Anatomy (the anatomy book, not the T.V. show) were created by me using some fairly advanced imaging techniques. If you are interested about some of the techniques, read my neuroimaging blog.

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The Hippocampus in 400 Words

Within the temporal lobe of the brain is an elongated structure called the hippocampus. Some people have compared its shape to that of a seahorse (the word hippocampus comes from the Greek {hippos + campos}, which roughly means “seahorse”). This structure is special for a number of reasons. One is its role in memory encoding and consolidation.

From cytoarchitectonic standpoint, the hippocampus is special because unlike the surrounding cortex, it consists of only three layers instead of six. The hippocampus is phylogenetically an old part of the cortex, which means that it is an older branch on the evolutionary tree, whereas the rest of the cortex (more accurately called the neocortex), especially cortex of the frontal lobes, is a much newer development.

The hippocampus resides within the medial portion of the temporal lobe. It is continuous with the parahippocampal cortex, entorhinal cortex (the hippocampus receives its main input from this cortex), and perirhinal cortex.

The hippocampus sends white matter tracts off its dorsal and posterior portions (the hippocampus also communicates through other tracts and pathways – this circuit is not the only output of the hippocampus). These white matter tracts are the fimbria of the hippocampus (technically, the fimbria are the “offshoots” of the alveus of the hippocampus). The fimbria proceeds upwards from the posterior portion of the hippocampus, at which point it ceases to be the fimbria and is called the fornix.

The fornices (plural of fornix) are prominent white matter tracts passing above the thalamus and medially in the brain. The fibers travel forward, then turn downward just posterior to the anterior commissure (a white matter tract that connects both hemispheres) to terminate in the mammillary bodies, two bumps on the ventral side of the brain. They are part of the hypothalamus of the brain. From there, the pathway courses upward through the mammilothalamic tract (MTT) to the anterior nucleus of the thalamus. From there axons course to the cingulate gyrus, then to the underlying cingulum (large white matter tract), and back to the hippocampus (via the parahippocampal and entorhinal cortices). This circuit is part of the limbic system and is called the Papez circuit. This circuit is important for emotion and memory.

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An Introduction to and Overview of the Brain

bi sang by seung ji baek

The human brain is a wondrous thing. It is the single most complex organ on the planet. It sits atop the spinal cord. Gazing upon the brain, one sees four main distinct areas – two roughly symmetrical hemispheres, a cerebellum stuck up underneath the posterior part of the brain, and a brainstem sticking out and down from the middle of the brain. Each cerebral hemisphere is divided into four visible lobes: frontal, temporal, parietal, and occipital. The frontal lobes jut out at nearly a 90 degree angle from the spinal cord and are the largest part of the human brain. The temporal lobes stick out the sides of the brain, like thumbs pointing forward at the side of a fist. The parietal lobes are harder to distinguish. They are just posterior to the frontal lobes and dorsal to (above) the temporal lobes. The occipital lobes are at the very back of the brain, like a caboose on a train.

The outside of the brain is covered with a series of bumps and grooves. The bumps are called gyri (sing. gyrus) whereas the grooves are called sulci (sing. sulcus). This outside part of the brain is filled with tiny cell bodies of neurons, the main functional cell of the brain. Some people estimate that there are 100 billion neurons in the central nervous system (brain + spinal cord). This outer layer of the brain is called the cortex (which means “bark”). The cortex is only about 5mm thick, or about the thickness of a stack of 50 sheets of copy paper, yet it is responsible for much of the processing of information in the brain.

At room temperature the brain is the consistency of warm cream cheese. If removed from the skull and placed on a table, it would flatten and widen out a bit, like jello that is warming up. The brain is encased in a series of protective sheaths called meninges. The outermost encasing is called the dura mater (L. “tough mother”), which is thick and tough and is attached to the skull. The next layer in is softer. It is called the arachnoid layer; it adheres to the brain. Just underneath this layer is where cerebrospinal fluid (CSF) flows. This fluid is produced in holes in the middle of the brain called ventricles. CSF helps cushion the brain as well as remove waste products from the brain. Underneath this is a very thin and fine layer called the pia mater (L. “soft mother”), which adheres directly to the cortex and is difficult or impossible to remove without damaging the cortex. These three layers of meninges serve to protect the brain.

The brain can be roughly split into three functional areas, each one more “advanced” than the previous. The brainstem (and midbrain), which includes such structures as the medulla, pons, and thalamus, activates and regulates the general arousal of the cortex. Damage to the brainstem often results in coma or death. The next rough functional area is the posterior portion of the brain (parietal and occipital lobes and portions of the temporal lobes). This area is heavily involved in sensory processing – touch, vision, hearing. It sends information to other parts of the brain largely through the midbrain structures. The last functional area includes the frontal lobes. This area can regulate all other parts of the brain but is essential for goal-setting, behavior inhibition, motor movements, and language. The frontal lobes are the most advanced area of the brain and arguably the most important for human functioning – for what makes us human. In summary the three areas roughly are responsible for:

  1. Overall arousal and regulation
  2. Sensory input
  3. Output, control, and planning

Underneath the cortex is a large area of the brain that looks white. This area is comprised of the axons of the neurons of the cortex and subcortical structures. These axons are the pathways between neurons – like superhighways connecting cities. The axons look white because the majority are covered with a fatty tissue called myelin. Myelin helps axons work more efficiently and transmit more quickly. The white matter of the brain is as important for normal brain functioning as the gray (neurons) matter is.

The brain is energy-hungry. It cannot store energy so it needs a constant supply of nutrients from blood. However, blood can be toxic* to neurons so the brain has to protect itself from the blood and other toxic materials through what is called the blood-brain barrier. This barrier keeps blood cells out of the brain but allows molecules of nutrients (e.g., glucose) to pass into or feed the cells. The entire surface of the brain is covered with blood vessels, with many smaller vessels penetrating deep into the brain to feed the subcortical structures. Deoxygenated blood must be removed from the brain. Veins take the blood out of the brain and drain into venous sinuses, which are part of the dura matter.

The brain works as a whole to help us sense, perceive, interact with, and understand our world around us. It is beautiful in its form and function.

*”Today, we accept the view that the BBB limits the entry of plasma components, red blood cells, and leukocytes into the brain. If they cross the BBB due to an ischemic injury, intracerebral hemorrhage, trauma, neurodegenerative process, inflammation, or vascular disorder, this typically generates neurotoxic products that can compromise synaptic and neuronal functions (Zlokovic, 2005, Hawkins and Davis, 2005 and Abbott et al., 2006).” From Zlokovic, B. V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 57(2), 178-201.

Image: Bi Sang by Seung Ji Baek

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Brodmann’s Map of the Cortex

I’ll be writing some basic neuroanatomy posts over the coming months (I started with my previous post about the corticospinal tract). I recently finished an intense neuroanatomy course where I learned how much I love basic neuroanatomy. It’s exciting to look at a brain or brain slices and try to figure out what and where different structures are.

In the early 1900s Korbinian Brodmann studied the cytoarchitecture (organization of the cortical layers of neurons) of human and non-human brains. His work was painstaking and thorough. He created a topographic map of the cortex containing 52 (50 in humans) different areas. In my class we were not required to learn all of Brodmann’s cortical areas but had to learn some of the major ones. Brodmann’s Areas (BA) 3,1, and 2 compose the primary somatosensory area of the brain. BA 4 is the primary motor cortex. BA 5 is somatosensory association cortex just posterior to BA 3,1,2. BA 6 is pre-motor cortex, which connects directly to BA 4. BA 7 is more somatosensory association cortex that lies just posterior to BA 5. BA 8 is the frontal eye fields, which among other things is responsible for initiating horizontal eye saccades (i.e., quick movement to the left or right). BA 17 is the primary visual cortex, a credit card sized area that lies both dorsal and ventral to the calcarine fissure in the occipital lobe. This area processes most of the basic visual information. BAs 18 and 19 are visual association cortices. BA 22 is Wernicke’s Area, which is involved in the comprehension of language and is in the dorsal-posterior temporal lobe on the border between the temporal and parietal lobes. BAs 41 and 42 are the primary auditory cortex, which processes auditory information from the cochlea; this lies on the transverse temporal gyrus in the dorsal part of the temporal lobes (it is hidden from view unless the cortex around the Sylvian Fissure is pulled away). BAs 44 & 45 are Broca’s area, which is involved in the production of language and is in the lateral frontal lobes.

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The Corticospinal Tract

The corticospinal tract is a descending motor pathway originating in the Primary Motor Cortex (Brodmann’s area 4) and terminating at various levels in the ventral horn of the spinal cord. The corticospinal tract descends through the posterior limb of the internal capsule then down through the cerebral peduncles into the brainstem. In the brainstem the corticospinal tract remains in the ventral portion, passing through the pyramids on its way down. In the caudal brainstem (just above where the spinal cord starts) 90% of the the corticospinal tract decussates (crosses) to the contralateral (opposite) side and continues down through the dorsolateral spinal cord. This portion controls limb movements. The remaining 10% remains in the ventral spinal cord and is largely responsible for bilateral axial (trunk) movement. From the dorsolateral spinal cord, the axon (that started in the cortex) enters the ventral horn of the spinal cord at the appropriate level (e.g., cervical for arms or lumbar for legs) then exits through the ventral root to terminate on the appropriate muscles.

Through this tract, the cortex controls much of the movement of the body; as such, it’s vitally important for our functioning. Damage to the tract results in an upper motor neuron disorder, with paresis (weakness instead of complete paralysis) and the Babinski reflex fairly common symptoms. Soon after damage, a patient might have flaccid paralysis though with little to no movement of the affected limb(s). As the body starts to recover slightly, spastic paralysis usually sets in with jerky, often uncontrolled limb movements. The corticospinal tract is one of the largest pathways in the central nervous system; it’s one of the most important for motor functioning as well.

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