axons – Brainy Behavior

June 26, 2011June 26, 2011

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.

July 15, 2009July 15, 2009

The Relationship Between Executive Function and Processing Speed

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.

October 2, 2008April 11, 2016

An Introduction to and Overview of the Brain

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:

Overall arousal and regulation
Sensory input
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