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.

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.

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.

Chronic Pain’s Impact on the Brain

Chronic pain is defined as pain that persists for longer than six months. This type of pain can affect a person’s cognitive abilities, emotional well-being, and overall quality of life. It can have a significant impact on the human brain.

One way in which chronic pain affects the brain is by altering its structure and function. Chronic pain can cause changes in the brain’s gray matter, which is the part of the brain responsible for processing sensory information, controlling movement, and controlling everything else we think. Brain changes associated with chronic pain can lead to a changed ability to process and interpret sensory information, as well as a changed ability to control movement. Difficulty concentrating, depression and anxiety, and some memory issues are possible with chronic pain.

Another way in which chronic pain can affect the brain is by altering its neurotransmitter systems. Neurotransmitters are chemical messengers that help transmit signals between neurons in the brain. Chronic pain can cause changes in the levels of neurotransmitters, including serotonin, dopamine, and norepinephrine, leading to an imbalance in the brain’s signaling system. This can result in a range of cognitive and emotional symptoms, such as difficulty with concentration and memory, irritability, and mood changes.

Chronic pain can also have a negative impact on a person’s emotional well-being. It can cause feelings of frustration, anxiety, and depression, which can further contribute to cognitive and emotional symptoms. This can lead to a decrease in overall quality of life, as well as an increased risk of developing mental health disorders such as depression and anxiety.

In conclusion, chronic pain can have a significant impact on the human brain. It can cause changes in the brain’s structure and function, alter its neurotransmitter system, and have negative effects on a person’s emotional well-being. It is important for individuals experiencing chronic pain to seek medical treatment and support to manage their symptoms and improve their overall quality of life.

Cognitive Rehabilitation Strengthens Brain Connections

There is increased interest in brain and cognitive rehabilitation to treat people with mild thinking and memory problems. Parkinson’s disease, while typically viewed as a neurodegenerative motor disorder, also affects thinking and memory. In a small clinical trial with Parkinson’s disease patients, patients received either occupational therapy or cognitive rehabilitation. Those who had cognitive rehabilitation showed increases in functional connectivity (a measure of time-linked correlations between changes in blood flow in different parts of the brain) between the left inferior temporal lobe and the left and right dorsolateral prefrontal cortex. These are brain areas important for a number of cognitive functions including memory, planning, and mental manipulation of information. If you need help to boost your mental health you can get brain supplements from Neuro Hacks, this can help optimize your brain performance. Those who did not receive cognitive intervention did not have increases in connectivity.

What does this mean for Parkinson’s disease and for cognitive rehabilitation? It’s difficult to say with this small study. It’s also unknown how long the changes last. Without a restructuring of the brain and continued cognitive rehabilitation it is not likely that the effects will last more than weeks or months after the rehabilitation ends.

To expand on this study (to bring in other research) and put things in simple terms, if people want to protect their brains they best they can as they age, they need to remain physically and mentally active and in good physical and mental shape. Learn new things. Travel to new locations. Take up a physically demanding hobby or dedicated exercise. This won’t solve all our aging problems but it will help a lot.

Reference

Díez-Cirarda, M., Ojeda, N., Peña, J. et al. Brain Imaging and Behavior (2016). doi:10.1007/s11682-016-9639-x

Memory Problems in Some With Parkinson’s Disease

From a recent news release by Jill Pease at the University of Florida.

Using a combination of neuropsychological testing and brain imaging, University of Florida researchers have discovered that in a group of recently-diagnosed patients with Parkinson’s disease, about one quarter have significant memory problems.

Parkinson’s disease is commonly known as a movement disorder that leads to tremors and muscle rigidity, but there is growing recognition of cognitive problems associated with the disease. One of the most common is slower thinking speed that causes patients to have trouble quickly retrieving information. The UF study identifies a subset of patients who have a different kind of cognitive issue — memory problems, or difficulty learning and retaining new information.

The findings were published July 24 in the journal PLOS ONE.

“While a large proportion of people with Parkinson’s will experience slower thinking speed, which may make them less quick to speak or have difficulty doing two things at once, we now know that there are a subset of individuals with Parkinson’s disease who have memory problems,” said Catherine Price, Ph.D., the study’s senior author and an associate professor in the UF College of Public Health and Health Professions’ department of clinical and health psychology, part of UF Health. “It is important to recognize which people have issues with learning and memory so we can improve diagnostic accuracy and determine if they would benefit from certain pharmaceutical or behavioral interventions.”

For the UF study, 40 people in the early stages of Parkinson’s disease and 40 healthy older adults completed neuropsychological assessments and verbal memory tests.

About half the participants with Parkinson’s disease struggled with an aspect of memory, such as learning and retaining information, or recalling verbal information, said lead author Jared Tanner, Ph.D., an assistant research professor in the UF department of clinical and health psychology who conducted the study as part of his dissertation research for a UF doctoral degree in clinical psychology.

“And then half of those participants, or nearly one quarter of all participants with Parkinson’s, were really having a difficult time consistently with their memory, enough that it would be noticeable to other people,” said Tanner, adding that researchers were encouraged by the fact that most participants in the initial stages of Parkinson’s were not having significant memory problems.

All participants received brain scans, which used new imaging techniques that allowed the scientists to navigate the pathways of white matter fibers, the tissue through which messages travel across the brain. The methodology was developed by the research group ofThomas Mareci, Ph.D., a professor of biochemistry and molecular biology in the UF College of Medicine, and is described in a paper published July 14 in PLOS ONE.

Experts have theorized that cognitive problems in Parkinson’s are caused by a shortage of the brain chemical dopamine, which is responsible for patients’ motor issues. But with the help of imaging, the UF researchers were able to spot changes in the brain’s gray and white matter that appear unrelated to dopamine loss and are specific to those patients with Parkinson’s who have memory problems.

“Not only is gray matter important for memory, in Parkinson’s disease white matter connections between the temporal lobe and a region in the posterior portion of the brain called the retrosplenial cortex were particularly important in the recall of verbal information,” Tanner said. “People with Parkinson’s disease who had stronger connections between these areas of the brain did better at remembering information.”

Tanner’s study is part of a larger research project supported by a $2.1 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Researchers led by Price are using imaging and cognitive testing to determine profiles for the cognitive problems that most commonly affect patients with Parkinson’s. The information gleaned from the research could help clinicians foreshadow the type of cognitive impairment a patient may experience over time, if any, and tailor treatment plans accordingly.

GABA receptor role in postoperative cognitive decline

About 20-30% of older adults (age greater than 60) undergoing major surgery experience temporary (generally reversed) memory and thinking deficits after major surgery, particularly heart and orthopedic. A small minority (<5%, probably much less) might not return to cognitive baseline (how they were before surgery). The cause of this decline in cognition is unclear, although many attribute it to the anesthesia used. So far, however, research has been inconclusive as to specific causes of cognitive difficulties after surgery. This is because surgeries are major events that affect most parts of the body, not just what is being operated upon. They are stressful – physically and emotionally.

Newly published research proposes one mechanism for causes of memory problems after surgery – anesthesia acting on ɣ-aminobutyric acid type A receptors (ɣ5GABAaR). This new research suggests that the function of these receptors does not return to baseline until much later than previously believed. This means that the normal function of chemicals in the brain, particularly ones important for memory, might be disrupted for longer than expected, and might play a role in memory problems that some individuals experience after major surgery.

Reference

Zurek, A. A., Yu, J., Wang, D. S., Haffey, S. C., Bridgwater, E. M., Penna, A., … & Orser, B. A. (2014). Sustained increase in ?5GABA A receptor function impairs memory after anesthesia. The Journal of clinical investigation, 124(12).

Modeling the Human Brain

Wired has an article about Dr. Henry Markram’s goal to simulate an entire human brain within 10 years. While his goal will not be met within that time-frame, this is important work to do. If we can have a way to simulate brain development or function, it can help us understand how brain disorders occur and help with the treatment of them.

One of the great things about the project is the collaborative nature of it: “‘But the only way you can find out is by building it,’ [Markram] says, ‘and just building a brain is an incredible biological discovery process.’ This is too big a job for just one lab, so Markram envisions an estimated 6,000 researchers around the world funneling data into his model…. Neuroscientists can spend a whole career on a single cell or molecule. Markram will grant them the opportunity and encouragement to band together and pursue the big questions.”

Read the Wired article for more information about the project and the 1 billion Euro grant Markham received.

Parkinson’s Disease and the Brain

The Michael J. Fox Foundation has a good, basic introduction to the neurobiology of Parkinson’s disease. The brief animate video provides an overview of affected parts of the brain as well as the role that dopamine, a neurotransmitter – a chemical in the brain that allows brain cells to communicate with each other – plays in Parkinson’s disease. Click on the link below and then click on the video link titled PARKINSON’S AND THE BRAIN to learn more about how Parkinson’s disease affects the brain.

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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.