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Parkinson’s Disease and the Brain

June 29th, 2011 No comments

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

June 26th, 2011 No comments

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.

Video Introduction to the Cingulum

September 15th, 2010 2 comments

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.

The Relationship Between Executive Function and Processing Speed

July 15th, 2009 1 comment

Understanding the relationship between brain (specifically subcortical structures) and cognitive processes is a field still in its infancy. The rise of structural and functional neuroimaging that started in the 1970s and really began to mature in the 1990s (with even greater changes and advancements being made today), led to the ability to measure the structure and function of various brain regions in vivo. This was and is important for neuropsychologists because it allowed them to more accurately assess the relationship between the brain and cognitive and behavioral functions.

Processing speed is a basic cognitive or brain processes that subserves many other higher-order cognitive domains. Among those higher domains is executive functioning, a somewhat broad construct that involves the organization of behaviors and behavior responses, selective attention of pertinent information and suppression of unnecessary information, and maintenance and shifting of cognitive sets. Thus, executive functioning is dependent on processing speed but processing speed is not dependent on executive functioning. If executive functioning is a car, processing speed is the engine. Having a faster or more powerful engine means that the car can go faster. More efficient engines allow the car to function at a higher level of efficiency. Thus, while processing speed and executive functions are distinct, they are related with processing speed as one of the basic cognitive processes driving executive functions.

As an example of the interaction between executive functions and processing speed in clinical applications we can look at the Stroop Color-Word task. A person who is not only able to read the words or name the colors quickly but also able to inhibit the undesired but automatic process (namely, word reading on the incongruent color-word task) will receive a higher score on the Stroop task. This would, in combination with other executive function tests, be evidence for intact or even good executive functioning.

Even on non-speeded executive tasks those with fast processing speed can benefit because they can sort through information more quickly and hopefully, efficiently – speed and efficiency are related but not exactly the same. However, not all tests of executive function rely on processing speed. A person, for example, could be slow on the Wisconsin Card Sort Test, yet not exhibit any “executive dysfunction” in that they could complete all the categories and not have an abnormal number of perseverative errors. This simply demonstrates that “executive functions” are diverse and varied.

As a basic process that is dependent on basic neuronal function and glial support, any sort of focal or diffuse injury to the brain can affect processing speed. An example of this is traumatic brain injury, which frequently results in diffuse axonal injury; this diffuse injury negatively affects cognitive processing speed. Any time the white matter is focally or grossly disrupted, processing speed is in danger of disruption itself. This disruption of white matter could be anything from axonal damage, loss of oligodendroglia (which form the myelin), or even low levels of neurotransmitters.

White matter disruption also occurs in multiple sclerosis where diffuse lesions are apparent in the white matter. This disruption also occurs more often in people with heightened vascular risk factors, such as hypertension, diabetes, and cardiovascular disease. People who have these vascular risk factors and subsequent damage to their white matter (this damage or disruption is frequently termed leukoaraiosis) have reduced processing speed and attention (Viana-Baptista et al., 2008). Lesions to subcortical structures, such as the caudate, also result in reduced processing speed (Benke et al., 2003) in addition to executive dysfunction.

In subcortical disease processes such as Huntington’s disease, which usually starts with atrophy of the caudate nuclei, or Parkinson’s disease, which starts with a loss of the majority of dopaminergic cells in the substantia nigra, processing speed is consistently affected. Some common symptoms of Parkinson’s disease are freezing and a shuffling gait; even though these symptoms are motoric, they can be indicative of the global cognitive slowing that also occurs. However, it seems that processing speed is heavily dependent on the integrity of white matter.

Because of the diffusivity of processing speed, I am not aware of any areas of the brain shown to be necessary for processing speed, outside of global white matter. As I mentioned above, damage to the caudate has been shown to affect processing speed but damage to almost any area of the brain, especially if the white matter is disrupted results in slowed processing speed. Neuropsychologists often talk about a patient who has executive dysfunction, slowed speed of processing, as well as some other cognitive deficits as exhibiting signs of a frontal-subcortical disruption – a frontal-subcortical profile. So far, no one has localized processing speed to a single area – many brain structures or areas affect it.

At this point, processing speed and executive functions cannot be “mapped” to separate basal ganglia structures or loops. Of the three classically recognized cortico-striato-thalamo-cortical loops involved in cognitive and emotional processes rather than basic motor processes, which were first introduced by Alexander, Delong, and Strick (1986), the dorsolateral prefrontal cortex circuit appears to be most correlated with processing speed (Mega & Cummings, 1994). This is also the circuit most strongly linked with executive functioning. It appears that rather than utilizing different circuits processing speed and executive functions utilize the same circuits; however, processing speed is much more globalized.

References

Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.

Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.

Mega, M. S., & Cummings, J. L. (1994). Frontal-subcortical circuits and neuropsychiatric disorders. The Journal of Neuropsychiatry and Clinical Neurosciences, 6, 358-370.

Viana-Baptista M, Bugalho P, Jordão C, Ferreira N, Ferreira A, Forjaz Secca M, Esperança-Pina JA, Ferro JM. (2008). Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. Journal of Neurology, 255, 360-366.

What is Executive Function?

July 10th, 2009 5 comments

Executive function is a term that describes a wide range of cognitive behaviors and processes. It is broad enough of a term that some people simply describe it as, “what the frontal lobes do.” When asked what exactly the frontal lobes do do, some revert to the circular definition of “executive functions.” However, executive functions are distinct from – but related to – what the frontal lobes do. The frontal lobes are involved in motor functions (e.g., pre-motor and primary motor areas), eye movement (e.g., frontal eye fields), memory (e.g., acetylcholine-producing portions of the basal forebrain), and language (BA 44,45 or Broca’s area). In addition, some executive functions incorporate areas of the brain outside the frontal lobes – the parietal lobes or basal ganglia, for example. Like many cognitive domains, executive functions are part of a distributed network of brain structures and regions.

Most neuropsychologists however, would define (or at least accept the following definition of) executive function similar to this: Executive function is the ability to selectively attend to, work with, and plan for specific information. This means that executive function is deciding what information, cognitions, or stimuli are relevant, holding and working with that information, and then planning what to do with it. As such, executive function is largely the roles of planning and organization. It is also the ability to recognize and learn patterns (i.e., cognitive sets) but also have the cognitive flexibility to respond to set changes and make a shift in set. Executive function also involves being able to select the appropriate response or behavior while at the same time inhibiting inappropriate responses or behaviors.

Executive functions have been compared to the conductor of an orchestra who, in order to make sense of the disparate instruments, sounds, and parts, must coordinate the members and lead the efforts of all the components of the orchestra. Executive functions also have been compared to chief executive officers of companies. These comparisons demonstrate that executive functions are arguably the most complex and highest of all cognitive functions. However, just like most other cognitive functions, executive functions are comprised of relatively simple processes (e.g., attention and processing speed) – it is just the unique combination of these more basic processes that makes executive functions so powerful.

One potential problem with executive function as a cognitive domain is that it is large and loose. Many tests have been developed, or at least used, to assess executive function (e.g., Wisconsin Cart Sort Test, Stroop Color-Word Task, clock drawing, and so forth). Even though all such tests are used as measures of executive functioning, scores on them do not always correlate highly with each other. They do not always cluster together when subjected to principal components analysis or even structural equations modeling. This means that even though neuropsychologists have many purported tests of executive function, they all seem to measure different aspects of executive function. This might partially result from executive functioning tests being differentially affected by basic cognitive processes such as processing speed.

Even though, as previously mentioned, I do not believe executive functions and frontal lobe functions are synonymous terms, are we able to localize executive functions to the frontal lobes? Largely we can. The most evidence from neuroimaging studies and neurological injuries demonstrate that the prefrontal cortex – the area of the brain that is phylogenetically youngest and most advanced and as such, proportionately larger in humans than any animal – is necessary (but not necessarily sufficient) for executive functioning. When this area is disrupted in humans, they exhibit poor decision-making skills, including poor planning and poor maintenance or self-regulation of behavior. One area of the prefrontal cortex particularly involved in executive functions is the dorsolateral prefrontal cortex (area 46) – although both the orbitofrontal and anterior cingulate are involved in aspects of executive functions.

In 1986 Alexander, Delong, and Strick published their seminal work on five parallel and closed cortico-striato-thalamo-cortical loops. These frontal-subcortical circuits were hypothesized to be involved in a range of behaviors and cognitions based on the varying cortical connections of the loops. Previously, many researchers did not well-understand the role that the basal ganglia played in any sort of “higher” function; in fact, most viewed the basal ganglia as involved mainly in motor behaviors. Alexander, Delong, and Strick’s article set off a flurry of research into the functions of these frontal-subcortical circuits, which have been verified as existent in humans (Middleton & Strick, 2000). Over time different theories have modified these circuits, including that they are composed of direct, indirect, and hyperdirect pathways, which all function at different speeds or timings to allow the basal ganglia to regulate behavior. Mink (1996) proposed that actions (e.g., producing a specific word) are regulated by the direct and indirect pathways, which serve as large components of our ability to select and inhibit correct and incorrect responses, respectively. It is as if each individual fronto-cortical loop allows us to properly attend to the correct behavior or response and inhibit all other behaviors or responses, much like the DLPFC and orbitofrontal cortex and their associated loops are involved in the selection and inhibition of behavior, both major aspects of executive function.

Just as damage to the dorsolateral prefrontal cortex (DLPFC) produces deficits in executive function, damage to any part of the DLPFC loop also results in executive dysfunction. Benke, Delazer, Bartha, and Auer (2003) presented two clinical cases of patients with left caudate lesions (the lesions also affected part of the anterior limb of the internal capsule as well as portions of the putamen and pallidum; however, the infarcts affected the caudate the most). Among other deficits, both patients had executive function impairments, including problem-solving deficits, many perseverative errors, and set-shifting problems. Even though the patients had no direct DLPFC damage, they exhibited similar deficits to patients with DLPFC lesions. These executive deficits persisted over time.

As a cognitive domain, and even as broad as it might be, executive functioning has ecological validity. Price and colleagues (2008) found that executive dysfunction was related to greater difficulty performing IADLs. Specifically, patients with executive dysfunction had more difficulty performing IADLs than patients with memory deficits did. Thus, how quickly, flexibly, and accurately people can organize, solve, plan, or attend to specific neuropsychological tasks seems to correlate with their accomplishment of everyday tasks of life, such as finances, driving, and shopping.

References

Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.

Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.

Middleton FA, & Strick PL. (2001). Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn., 42, 183-200.

Mink, J. W. (1996). The basal ganglia: Focused selection and inhibition of competing motor programs. Prog Neurobiol, 50, 381-425.

Price, C.C., Garvan, C., and Monk, T. (2008). Type and severity of cognitive impairment in older adults after non-cardiac surgery. Anesthesiology, 108, 8-17.

PBS Frontline Explores Parkinson’s Disease

February 7th, 2009 2 comments

Here is the video PBS recently made about Parkinson’s disease called My Father, My Brother, and Me. From what I’ve watched so far, it’s done a good job putting a face to Parkinson’s disease while also focusing on the research and clinical aspects of it.

Hippocampus Anatomy Video

November 18th, 2008 No comments

To follow up my previous post on the hippocampus, here’s a video posted by drbobrd on YouTube. He uses a model of a brain to explain some brain anatomy, including the hippocampus and fornix.

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The Hippocampus in 400 Words

November 18th, 2008 No comments

I have to apologize for the paucity of posts on this blog. The grind of my semester got to me. After a few week break it’s time for a neuroanatomy post.

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 (to be more accurate, there are two hippocampi – one in each cerebral hemisphere) 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. I’ll not write about the internal structure of the hippocampus, which becomes fairly complex, due to the brief nature of this post.

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 (pronounced “papes” – rhymes with capes) circuit. This circuit is important for emotion (and memory).

An Introduction to and Overview of the Brain

October 2nd, 2008 1 comment

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 itself is toxic to neurons so the brain has to protect itself from the blood 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.

Image: Bi Sang by Seung Ji Baek

Brodmann’s Map of the Cortex

September 2nd, 2008 No comments

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.