Tag: neuroscience

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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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The Necessity of Psychotherapy

Years ago I wrote an essay about the death of psychotherapy. While I did not state that psychotherapy is currently dead, I did state that much of it might die in the wake of advances in understanding the neurobiology of psychological disorders. It will take decades for these advances to occur (if they ever do) so this post will now serve to balance my post from years ago.

I’m going to start with a story about two people (these are based on real events but names, situations, and identifying details have been changed to protect confidentiality). Jim was convicted of a violent crime and spent a number of years in prison. He was required to attend treatment throughout his years in prison – anger management and other therapies. He had a history of alcohol and drug abuse. A while after he got out of prison, he started therapy again to help him through some difficulties, including his experiences with homelessness. Jim was a very pleasant person to interact with; he was well-read and insightful. He was trying to improve his life.

The second person was named Frank. He was also homeless but was staying with a friend. He had past drug and alcohol abuse but had been free from drugs for about a year. He was anxious, paranoid, and not the most pleasant person to interact with. He had never received treatment for depression, which he experienced chronically and severely. He exhibited little insight into his problems. He thought the negative events in his life were all someone or something else’s fault.

The first patient had learned a lot from his psychotherapy over the years. The second never had therapy. While they were very different people, they experienced similar challenges and psychological issues over the years. Without disregarding individual differences, the patient who had had years of therapy had a lot of insight and self-knowledge but the other patient had very little.

Jim had been a violent man but over the years and through therapy, he learned a great deal of self-control and restraint. Psychotropic medications could not have taught Jim this. For him, psychotherapy was highly successful. Without out it he might not have been the pleasant person that he was.

Therapy teaches you skills; it gives you tools to deal with maladaptive thoughts and behaviors. It allows you opportunity to sort through your experiences and thoughts in a safe place. It allows to to talk to someone else without being judged. Therapy is thus treatment and education. It can have as strong or stronger effects on mood and behavior as medications and the benefits can last longer. Understanding biology is necessary to understand behavior but it is not sufficient to explain all behavior, at least not with our current knowledge. Will we ever had sufficiently advanced knowledge of neuroscience and biology to no longer need psychotherapy? I don’t know but if we do, it won’t happen for many years.

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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).

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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.

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Intelligence and Neurological Conditions

Intelligence is an interesting concept. We have tests that measure what we call intelligence but such tests are limited and culture-centric (not that that is necessarily a negative thing). However, for the sake of discussion I will operationally define aptitude (i.e., intelligence) as Intelligence Quotient so as to have a standard metric as foundation for this post.

I spend time assessing people’s memory and thinking abilities. I almost always try to get some measure of baseline aptitude either by estimating it (e.g., years of education, vocabulary knowledge, word reading ability) or by formally measuring via an intelligence test. Granted, this has limitations but it allows me to estimate how well an individual’s brain should function across multiple domains of thinking (e.g., problem-solving, reasoning, memory, language, and so forth). In other words, the higher a person’s general aptitude (abilities), the better he generally will do across most cognitive domains barring brain insult. This is certainly not a rule codified in stone and in triplicate but it serves as a rubric to follow.

Intelligence as measured by IQ is generally quite stable across the lifespan but can improve modestly with  diligence in informal or formal education. Intelligence as denoted by IQ can also decrease modestly if people are intellectually inactive, although such declines are slight. What can happen though is as brains age or if damaged by a pathological process or an injury, components of IQ can decrease. My primary clinical and research focus is in understanding how brains and cognition change in old age – both naturally and in the presence of neurological (brain) insult. Remarkably, the measures we use for intelligence tend to be rather insensitive to aging and even neurological insult, at least some of the components of intelligence are generally insensitive to brain insult. However, this leads to one area where our conceptualization of intelligence as IQ starts to break down.

As they age, the brains of people almost universally slow down. Wear and tear on the brain over decades of life affects how well and quickly we can think. Blood, which is essential for life and for the functioning of the brain, happens to be toxic to brain cells. Sometimes the protections in the brain that keep blood far enough from brain cells (neurons) to protect them but near enough to feed and maintain brain cells start to break down over time. This can injure the brain and start to reduce how well the brain works, even lowering IQ. Now, does that mean that a person’s intelligence decreases? If IQ = intelligence, then yes, it does. Contrary to how I operationalized intelligence earlier, intelligence is not synonymous with IQ. IQ can be a useful concept but it is far from perfect, particularly if by using it one argues that someone is less intelligent simply because his head was injured in an accident or because she developed dementia or suffered a stroke.

This is an area that demonstrates the limitations of our current research and clinical conceptualizations of intelligence. However, understanding how IQ changes over time and how it is affected by neurological conditions is important information to have, as it can help localize areas of pathology.

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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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Can We Cure Parkinson’s Disease?

The National Parkinson’s Foundation produced a series of brief videos providing overviews of Parkinson’s disease related topics by prominent clinicians and researchers in the field of Parkinson’s disease. In one video, we are provided with an overview of the questions of whether or not we can cure Parkinson’s disease and how do we treat Parkinson’s disease.

The short answer is: no, we cannot right now cure Parkinson’s disease. We have hopes that stem cell therapies will work but there are a number of issues related to stem cells that make them potentially problematic (e.g., how do we make sure they don’t turn into cancers).

We can, however, treat symptoms of Parkinson’s disease with drug, physical, and cognitive therapies. L-dopa is effective at reducing tremors in most people and well as increasing rate and speed of movement. In some cases, deep brain stimulation is warranted. It has shown to be quite effective for many people. But for now we cannot cure Parkinson’s disease.

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Mad Cow And Alzheimer’s Have Surprising Link : NPR

Mad Cow And Alzheimer’s Have Surprising Link : NPR. If this research showing a link between prion proteins and the deleterious effects of beta-amyloid plaques in rat brains holds true in humans, it has huge implications for finding a cure for Alzheimer’s disease. That would be as big as the polio vaccine or eradicating small pox. This is some research that is worth watching closely.

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The Death of Psychotherapy

I’m going to preface my post by stating that the following post was written to help me think through the relationship between neuroscience and therapy. As such, it is a philosophical journey through some of my thoughts and is not even necessarily what I really believe because I’m still working on discovering what I believe. Thought processes like this are one way I try to keep some of my beliefs about psychology and neuroscience balanced. If I start leaning too strongly one way, I’ll start looking for things that disconfirm those beliefs and see what I discover. It’s a bit of playing the Devil’s Advocate with myself and a bit of philosophizing. Some of my friends and I used to do things like this in junior high and high school – having philosophical discussions where we discussed things and even tried to argue for things that we didn’t necessarily believe (e.g., classic topics such as supposing that this world and universe really aren’t real but are just reflections of reality. Again, that’s not something I believe but we would speculate). What does this all have to do with psychology and neuroscience?

The brain is what drew me to psychology initially. However, I vowed I would never go into clinical psychology because I didn’t think I would like therapy or dealing with people’s problems. Over time I discovered neuropsychology. Most neuropsychologists are clinical psychologists so in order or me to be a neuropsychologist, I had to be trained as a clinical psychologist. There are many things I enjoy about clinical psychology but therapy is not one of those things. Granted, most neuropsychologists do not actually do therapy, but we have to be trained in it. I enjoy talking with people in sessions but I haven’t been that impressed with therapy as a whole so far. Maybe that’s just because I haven’t exactly found the particular type of therapeutic method that really “clicks” with me. Cognitive-behavioral therapy is fine but so much of actual therapy in practice is just plain common sense. However, not everyone has a lot of common sense so they need some training in it. Part of me recognizes the validity of therapy but another part of me struggles with it. Now on to my main article.

The more I study the brain and the more exposure I have to therapy (giving, not receiving), the more biased towards the brain I become. What I mean is that we continue to discover more about the brain and as we discover more, the more behavior we can explain based on biology or neurophysiology and the less important I think therapy is. I’ve written about this topic in the past but wanted to briefly revisit it. This is somewhat of a second chapter to that post. Before I continue I wanted to expose one of my biases; I believe humans have free will. Even though some of my beliefs about the brain could be seen as mechanistic and deterministic, I do not believe that a strongly-biological foundation for behavior rules out free will. You can still assume biological foundations without assuming determinism. If, for example, you have a monistic set of assumptions that incorporates both mind – “nonmaterial” – and body – “material” – in one. [I have quotes around nonmaterial and material because mind is not necessarily nonmaterial and body is not necessarily material, well at least philosophically speaking]. Monism is a similar idea to a unified field theory (e.g., Grand Unified Theory) or the Theory of Everything for which some theoretical physicists are searching. That’s not what I’m going to write about and if it didn’t make sense, then don’t worry about it (I discussed this topic in a couple different posts: here {I linked to that post previously} and here). To summarize, I view behavior through a strong biological bias but I do not assume determinism.

As I said earlier, the more I learn about the brain and behavior (through research and observation), the more I lean towards neuroscience and away from “traditional psychology.” However, I still appreciate the psychosocial aspects of behavior; the nature versus nurture dispute will never be resolved because both are important. The environment is important  – all external stimuli are important – but the problem with downplaying biology is that it is the medium of behavior. What I mean is, everything we think, sense, perceive, or do is translated and transmitted through the firing of neurons. This means that all abnormal behavior, which is what psychologists often are interested in, originates in a neuron or related cell. Whether or not the cause of that behavior was internal or external is irrelevant. All events and stimuli are translated into patterns of neuronal firings.

This is why I think that understanding the biology of the brain is the best way to understand a person’s behavior. However, because we have an imperfect understanding of the biology of the brain, we have an imperfect understand of the biological foundations of behavior. This means that until we have a perfect understanding, we cannot ignore the psychosocial aspects of behavior; even with a perfect understand we couldn’t either because even if we understand the “translation” process we may not understand the origin of what needs to be translated. This is where traditional talk therapy can be most beneficial. However, I still believe less and less that talk therapy is the best solution for dealing with many psychological issues. Over time as we discover more and more about the brain, therapy will become even less important.

That is a fairly radical position to take as a student of clinical psychology – it’s more in line with psychiatry, or rather, I believe it’s more in line with neuroscience. I’m not saying that therapy is useless, I’m just saying that as we gain a more perfect understanding of the brain and how various chemicals interact in the brain, we will have less need for people to help others by “talking” through their problems. The better we understand the physiology of the brain, the more natural our pharmaceuticals will be. In other words, it will be easier to mimic and create normal brain functioning. Of course, many will ask, “What is normal?” That’s a good question.

Some may argue that with depression, for example, many people will have negative image and self-evaluations, which can lead to depression. That is true but it’s the classic chicken and egg question. Which came first? Did the negative thoughts cause the depression or did the person experiencing negative thoughts have a biological predisposition to those thoughts and depression? In other words, it is possible that biology originally led to the negative thoughts and not vice versa. This is all speculation but I think there is increasing evidence for this view.

The big problem with my point though is that at some point, it does become a deterministic system in that it’s possible that we could medicate away people’s free will. This is an unacceptable outcome. There would be a lot of power with this knowledge and many opportunities for abuse. That’s an ethical discussion for a later time.

To summarize, I think that as we (speaking in the collective) gain a more perfect understanding of the brain (and even individual differences in the brain) we will be better able to eradicate and prevent many or most psychological disorders. We could potentially stop schizophrenia through genetic engineering or other modifications. Again, I’m not addressing whether or not we should but I believe we will have the ability to at some point. This is why, at the moment I lean more towards neuroscience than I do psychotherapy. Of course, tomorrow I could [I won’t] write a post that completely contradicts this one. As I said, this is a process. I think it’s important to argue both sides of the issue.

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