Brainy Behavior

I’ve been developing an interest in the role that the frontal lobes play in memory. We traditionally think of memory as heavily based in the medial temporal lobes. At least, the medial temporal lobes are larely responsible for the creation of new memories. Without the hippocampus and the surrounding area people have anterograde amnesia, which is the inability to form new memories. The classic and most well known example of this is the patient H.M. Researchers recognize the role that other areas of the brain have in memory but most memory research has focused on the medial temporal lobes – at least until recently (with recently being the last 20 years or so). New ideas take a while to develop and gain acceptance so some of these ideas about the role of other brain areas in memory creation are still developing.

For example, we now know that when information needs to be organized, such as in something like the Rey-Osterrieth Complex Figure (read here for a short description of the test) or with a list learning task with words from specific semantic categories, the frontal lobes are involved.

If the frontal lobes are heavily involved in the organization of information it follows that memory tests that require more organization of material should be affected by dysfunctioning of the frontal lobes. Some researchers are now trying to place certain functions with greater specificity within the frontal lobes. This isn’t really phrenology because the methods of phrenology were entirely suspect. Phrenologists extrapolated personality and cognitive characteristics of people based of measurements of their skulls. Many researchers who are interested in localizing brain functions do so by testing people with specific brain

lesions (injuries). If enough patients have damage to X part of the brain and subsequently have Y deficits, then we can assume that X is necessary for Y to occur (but is not necessarily sufficient for Y to occur). Phrenologists never looked at the brain or the head in this manner. Paul Broca was one of the first, with his patient Tan, to systematically look at the relationship between brain injury and behavior.

For a long time many people believed (and many still do) that certain areas of the frontal lobes, specifically the most anterior areas of the frontal lobes, are essentially superfluous. They base this idea on cases where

people have had damage to this area of the brain but apparently suffered no ill effects. Research has consistently not supported that view. We don’t have any non-necessary brain. What we do have are tests and measures that are not sufficiently sensitive nor specific. The brain is also very complex and most functions rely on networks of brain structures. We are also learning that the white matter in the brain is very involved in behavior and cognition (this is my own area of research). The more we learn, the more we realize our ignorance about the brain. There are layers upon layers to be unwrapped and understood about the brain.

Image by Debbi in California.

As people age, it is common for their brain white matter to change. These changes often appear as bright white spots on T2-weighted MR scans. These areas or spots of hyperintensity (i.e., white matter hyperintensities {WMH}) are also called leukoaraiosis (LA). Researchers are still investigating the exact nature and pathology of these abnormalities but our understanding of them is increasing. They most often seem to start around the lateral ventricles and spread from there, although it is possible to have punctate WMH throughout the brain white matter (i.e., WMH that are not connected to other regions). WMH on brain MRIs represent rarefaction of the white matter, including swelling, demyelination, and damage, although the exact nature and combination of the white matter changes is not known. These WMH can interfere with normal cognitive functioning, including processing speed, attention, inhibition, as well as global executive functioning (although these claims are still being investigated).

Other damage to white matter includes lacunes, which are little holes in the brain, much like the holes in Swiss cheese. They are caused by mini infarcts, or strokes, or other processes. Most of the time they are due to “silent strokes”, or strokes that are small enough that the person does not have any noticeable stroke symptoms. These lacunes can have similar impact on cognition as WMH. Both WMH and lacunes are related to vascular risk factors, such as hyper- or hypo-tension, diabetes, etc.

Parkinson’s disease (PD) affects an estimated 1.5 million Americans and about 2% of people over 65 in the U.K. Its prevalence increases with age, although roughly 15% of Americans with Parkinson’s disease are 50 or younger. Parkinson’s disease is part of a broader spectrum of disorders known as parkinsonism. While it was viewed as fairly homogeneous in the past, researchers and clinicians now recognize the complexity of the disease and its related diseases.

The defining neurological marker of Parkinson’s disease is the destruction of the substantia nigra pars compacta, a small nucleus in the brain that is one of the major dopamine-producing brain areas. Symptoms of PD are not evident until around 80% of the neurons in the substantia nigra (literally translated as “black substance”) are destroyed. Because the substantia nigra produces dopamine, which is an important neurotransmitter, the depletion of dopamine in the brain that is associated with PD affects the striatum, which in part suppresses the subthalamic nucleus. This in turn results in more activity in the globus pallidus and substantia nigra pars reticulata, which in the end leads to more activation of the inhibitory thalamic nuclei that are involved in motor functioning. To summarize, decreased dopamine results in decreased motor activation as well as other motor problems.

The common features of Parkinson’s disease are easily remembered by the mnemonic TRAP.

1. T – Tremor, specifically resting tremor. Tremor that occurs when moving (e.g., reaching for an object) is called essential tremor and is not a defining characteristic of PD; in fact, it is a different but related disorder.
2. R – Rigidity. Difficulty moving and stiff arms and limbs.
3. A – Akinesia. No or slow movements.
4. P – Postural instability. Posture problems.

Gait abnormalities is also one of the common features of PD. It is especially useful for detecting the disease early in the process. The common gait problems are decrease height and length of step and less arm swing (i.e., walking more with a shuffle than a normal gait). People with PD also often take very small steps when turning around.

PD patients often have difficulty swallowing saliva so they often drool. They also often have micrography (very small writing) that progressively gets smaller with prolonged writing. Depression is common in PD patients as well. If given levodopa (L-dopa) they will respond. Symptoms of dementia often occur as well but they usually occur after a few years post diagnosis. However, there are often more mild cognitive changes early on in the disease process, such as slowed processing speed and slowed reaction time.

Reference

Approach to diagnosis of Parkinson disease (C. Frank, G. Pari, & J. P. Rossiter, 2006). Canadian Family Physician, 52, 862-868.

I saw an interesting case today. It was a child with a hypothalamic hamartoma, a tumor (likely present from birth or shortly thereafter) right on the midline of the brain by the hypothalamus and the third ventricle. These tumors are quite rare and result in some interesting behaviors. A common result of these hamartomas is what is called precocious puberty – very early puberty onset; this early puberty often occurs before age 2. This can occur because the hypothalamus is one of the major brain areas that creates hormones and modulates the endocrine system.

Another common result of these hamartomas is gelastic seizures. Gelastic seizures are laughing seizures. The seizure manifests with the child (or adult) having sudden laughing fits for no apparent reason. They can occur many times a day. Some people also have dacrystic seizures, or crying seizures. Developmental delays are also common in this type of brain disorder as is hyperactive behavior.

Hypothalamic hamartomas are sometimes treatable by resection. This surgery has the possibility of eliminating the seizures and stopping most or all of the hormonal abnormalities.

I read a good article on CNN that details some of the problems that veterans and health professionals face when dealing with TBIs acquired during military action. The article provides a good perspective of the “human side” of TBI.

Link to the story

I’ve posted about this topic before but felt that we should revisit it because so many veterans are affected by TBIs (as well as mental health issues). I don’t know the exact number of veterans affected by TBIs but studies have shown that >30% of soldiers and Marines have some sort of psychological issue related to their service in Iraq and/or Afghanistan. The military and the government are realizing how salient this problem is and will be.

“Congress included $900 million in the DoD’s supplemental budget fir fuscal years 2007 and 2008 to fund more mental health services, as well as more research on the effects of traumatic brain injuries (TBI) and treatments for TBI and post-traumatic stress disorder (PTSD)” (Monitor on Psychology, Sep. 2007, pp. 38-39).

If you were like me a few years ago I had no idea what clinical neuropsychology was. I guess I should first start out with what clinical psychology is and how it differs from other disciplines. One common misconception that I run across is that I am studying to be a psychiatrist. Nope, psychologists are different from psychiatrists. Psychiatrists go to medical school, receive an MD, and specialize in psychological disorders after that. Since they are MDs they can prescribe drugs (and often believe – if I can stereotype – that drugs are pretty close to panaceas). Psychologists earn PhDs (or, PsyDs) in the United States from clinical psychology programs. After grad school and an internship, psychologists need to pass the licensing exam in a state to be able to see clients and patients.

Neuropsychologists specialize in brain functioning and typically see clients with brain disorders. The problems can range from epilepsy to autism to learning disorders to traumatic brain injuries to dementias. Neuropsychologists generally want to understand how brain (dys)function affects performance on various tests. Conversely, they believe that test performance reaveals much about how the brain is or isn’t working and where any damage might be. Neuropsychologists also commonly use MRIs and other brain imaging techniques to provide more information about their clients.

What are the job options for someone with a PhD in Clinical Psychology (emphasizing neuropsychology)? There is always academia, where research and teaching are king. Many neuropsychologists in academia also see patients clinically. Neuropsychologists can also work in hospitals, clinics, or private practice. A number conduct forensic evaluations for legal cases (e.g., work-related injuries, automobile collisions, etc.). The military also employs a number of neuropsychologists. Some neuropsychologists also work for business or governmental agencies as consultants, statisticians, or psychologists. While psychologists do not make as much money as MDs, they generally are paid well, have good hours, and good job security.

Time has a nice article about obsessive-compulsive disorder (OCD) titled “When worry hijacks the brain.” Like most articles by journalists, it’s a bit melodramatic (e.g., “Even the most stable brain operates just a millimeter from madness”) at times but overall it is a nice introduction to OCD and the biology (neuroscience) behind the disorder.

CNN posted an interesting article about how when people choose to be charitable (i.e., give money away) that the nucleus accumbens, which is termed the “pleasure center” of the brain, and the caudate nucleus showed heightened activity. It’s turning out that the nucleus accumbens is involved in far more activities than we’ve ever realized. It’s an area of the brain that is heavily tied to the dopaminergic system and is directly tied to drug use, eating, sex, and pretty much anything else that people can enjoy. In addition, assumed dysfunction or dysregulation of the nucleus accumbens is tied to addictive behaviors. It’s not surprising then that a behavior that is enjoyable to so many – being charitable – is related to activity in the nucleus accumbens. Maybe some people are just Scrooges because they have too little dopamine in their brains [pure speculation and meant to be slightly humorous but it is a hypothesis that could be worth testing].

Image courtesy of benevolink

An article in the most recent Monitor on Psychology (published by the American Psychological Association) [here's a link to the article that is accessible for free online: Link) reminded me of something one of my professors in graduate school told our class a couple years ago. He is a clinical neuropsychologist who occasionally does some consulting for the military. After he returned from a consultation with the military he told us that between the war in Afghanistan and the Iraq war there had been 18,000 central nervous system (brain and spinal cord) injuries of soldiers and contract employees serving in those two countries. The majority of the injuries were minor and many were not combat related but there are still thousands of people with moderate to severe CNS injuries that were acquired in war zones. Quoting from the Monitor article:

"Psychologists, particularly neuropsychologists, are stepping in to assess the damage, help patients learn new strategies to compensate while their brains recover, and raise public awareness of the increasing number of servicemen and women with TBIs. In fact, 1,977 service members were treated for them at Defense and Veterans Brain Injury Center (DVBIC) sites from January 2003 to February 2007."

One reason for high rates of traumatic brain injury in the Iraq (and Afghanistan) war(s) is the improved (compared to previous wars) body armor and other life-saving devices. The downside to fewer fatalities is that there are higher rates of people with severe injuries who survive. The mild TBI rates are shown to be: "between 10 and 20 percent [in some surveys] of soldiers returning from deployments” (Source). It’s great to have fewer fatalities but TBIs can have profound effects on people. Clinical neuropsychologists can help people with TBIs learn how to best cope with their injuries as well as understand how their lives might be different and what they can do to compensate for any difficulties. Most people with mild to moderate TBIs seem to have complete or nearly complete recoveries; however, those with moderate to severe TBIs may have deficits, many very severe, that last the rest of their lives.

There can be myriad short-term problems associated with TBIs (e.g., mental slowing, memory problems, personality changes, concentration and attentional difficulties, etc.) but there are also long-term ones. Research has shown that a person with a history of multiple TBIs is more likely to get Alzheimer’s Disease in old age (well, the research actually shows that there is an over-representation of people with multiple TBIs in the Alzheimer’s population). There is a great need for clinical neuropsychologists currently and in the future to work with and help all of our war veterans who have acquired brain injuries.

Acute respiratory distress syndrome is a common cause of mortality and morbidity, affecting an estimated 150,000 people per year in the United States (Rubenfeld, Doyle, & Matthay, 1995) however, recent evidence suggests the incidence may be higher (Rubenfeld, 2003). Compared to 20 years ago mortality has decreased from 80% to 30% of ARDS participants (Milberg, Davis, Steinberg, & Hudson, 1995; Brower et al., 2000) resulting in approximately 100,000 people who survive ARDS each year in the United States (Bersten, Edibam, Hunt, & Moran, 2002). Acute respiratory distress syndrome occurs in response to a variety of insults including sepsis, trauma, pneumonia, massive transfusion and other medical/surgical conditions. Treatment of ARDS requires aggressive supportive care including positive pressure ventilation (Brower et al., 2000) and increased oxygen concentrations with risks of barotrauma, oxygen toxicity, and nosocomial infection.

Acute respiratory distress syndrome may be a consequence of multiple organ system dysfunction, including the central nervous system (Bell, Coalson, Smith, & Johanson, 1983; Montgomery, Stager, Carrico, & Hudson, 1985). Participants who survive ARDS are at risk for neuropsychological deficits (Hopkins et al., 1999; Rothenhausler, Ehrentraut, Schelling, & Kapfhammer, 2001; Al-Saidi et al., 2003; Hopkins, Weaver, Chan, & Orme, 2004) 6 to 12 months following hospital discharge. Approximately 33% of general medical ICU survivors, some with ARDS, have cognitive impairments (Jackson et al., 2003) 6 months after hospital discharge. In 1999, Hopkins and colleagues found that 45% of ARDS survivors had neurocognitive impairments including impaired memory, attention, concentration, mental processing speed, and global intellectual decline one year post-discharge.

Others have since made similar observations (Marquis et al. 2000; Rothenhausler et al., 2001; Al-Saidi et al., 2003; Jackson et al., 2003). The prevalence of neurocognitive impairments varies from 25% (Rothenhausler et al., 2001) to 78% in participants with more severe ARDS (Hopkins et al., 1999). Neurocognitive impairments are a major determinant in return to work, work productivity, and life satisfaction following ARDS (Rothenhausler et al., 2001).

 References

Al-Saidi, F., McAndrews, M. P., Cheunt, A. M., Tansey, C. M., Matte-Martyn, A., Diaz-Granados, N., et al. (2003). Neuropsychological sequelae in ARDS survivors. American Journal of Respiratory and Critical Care Medicine, 167, A737.

Bell, R. C., Coalson, J. J., Smith, J. D., & Johanson, W. G., Jr. (1983). Multiple organ system failure and infection in adult respiratory distress syndrome. Annals of Internal Medicine, 99, 293–298.

Bersten, A. D., Edibam, C., Hunt, T., & Moran, J. (2002). Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. American Journal of Respiratory and Critical Care Medicine, 165, 443–448.

Brower, R. G., Matthay, M. A., Morris, A., Schoenfeld, D., Thompson, B. T., & Wheeler, A. (2000). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine, 342, 1301–1308.

Hopkins, R. O., Weaver, L. K., Chan, K. J., & Orme, J. F. (2004). Quality of life, emotional, and cognitive function following acute respiratory distress syndrome. Journal of the International Neuropsychological Society, 10, 1005–1017.

Hopkins, R. O., Weaver, L. K., Pope, D., Orme, J. F., Bigler, E. D., & Larson-Lohr, V. (1999). Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine, 160, 50–56.

Jackson, J. C., Hart, R. P., Gordon, S. M., Shintani, A., Truman, B., May, L., et al. (2003). Six-month neuropsychological outcome of medical intensive care unit participants. Critical Care Medicine, 31, 1226–1234.

Marquis, K., Curtis, J., Caldwell, E., Davidson, T., Davis, J., Sanchez, P., et al. (2000). Neuropsychological sequelae in survivors of ARDS compared with critically ill control participants. American Journal of Respiratory and Critical Care Medicine, 161, A383.

Milberg, J. A., Davis, D. R., Steinberg, K. P., & Hudson, L. D. (1995). Improved survival of participants with acute respiratory distress syndrome (ARDS): 1983-1993. Journal of the American Medical Association, 273, 306–309.

Montgomery, A. B., Stager, M. A., Carrico, C. J., & Hudson, L. D. (1985). Causes of mortality in participants with the adult respiratory distress syndrome. American Review of Respiratory Disease, 132, 485–489.

Rothenhausler, H. B., Ehrentraut, S., Stoll, C., Schelling, G., & Kapfhammer, H. P. (2001). The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: Results of an exploratory study. General Hospital Psychiatry, 23, 90–96.

Rubenfeld, G. D. (2003). Epidemiology of acute lung injury. Critical Care Medicine, 31, S276–S284.

Rubenfeld, G. D., Doyle, R. L., & Matthay, M. A. (1995). Evaluation of definitions of ARDS. American Journal of Respiratory and Critical Care Medicine, 151, 1270–1271.