Faculty Member Shares Brain Research in IDS Class

Rivers science teacher Maureen Courtney took time out from her year-long leave of absence to talk to students in Dave Burzillo’s Pathogens, People, and Inequality class before spring break. Courtney shared the results of the research project that she has been working on as a doctoral candidate at Boston University. The talk gave students not only an understanding of her study of HIV-associated dementia, but also a glimpse into the arduous process of researching, writing, and defending a doctoral dissertation.
 
“There are few aspects of human culture and society that have not been touched by infectious disease, from Old Testament plagues to more recent outbreaks like Ebola and Zika,” commented Burzillo. “Historians have written extensively about the impact of disease on cities and population groups, on government and public health policy, and on economics in general. This Interdisciplinary Studies course gives them a sense of what is going on in this exciting field.”
 
“The course asks students to examine the impact of infectious disease on humans through the lenses of biology, history, and ethics. We begin the course by exploring the biology of disease, taking an in-depth look at bacteria and viruses and their role in causing disease,” Burzillo continued. “Then students focus on case studies of plague, smallpox, and influenza to help them understand the historical, political, social, and economic impact of infectious disease outbreaks on human populations. The course concludes with a final project where students are asked to draw on what they have learned in each of the previous units of the course to examine HIV/AIDS from biological, historical, and ethical perspectives.”
 
Rivers’ IDS courses rely on both the school’s faculty as well as invited guests to help students explore the significant connections between the various disciplines their content encompasses. In this case, by sharing her cutting-edge research on HIV/AIDS, Courtney provided the students with a neuroscientific approach that students would otherwise have not gotten.
 
In the 1980s and early 90s it was common for people with HIV to develop AIDS and die in a very short span of time," said Burzillo. "With the development of antiretroviral drugs, people with HIV have been able to live much longer before developing AIDS—or they haven’t developed AIDS at all. Drugs are instrumental in fending off pneumonia and other opportunistic infections, but they can’t protect the human brain from HIV, and doctors are seeing the development of symptoms that did not have time to develop in the 1980s. AIDS-related dementia is one of those symptoms. As a result, Courtney’s work is very novel in its focus.”
 
“The brain hates blood," Courtney told the class. "While blood plays a critical role in carrying oxygen to the brain, direct contact between blood and brain cells (or neurons) causes severe damage. Without oxygen delivery to the brain, neurons begin to die, leading to a stroke. If a blood vessel leaks or a brain aneurysm bursts, the meeting of neurons and blood results in devastating swelling and pressure within the brain. To keep the oxygen flowing, but the neurons safe, we have a built-in filtering mechanism called the blood-brain barrier that separates the circulating blood from the fluid that surrounds our neurons. The blood-brain barrier also protects the brain from other threats and neurotoxins, but HIV has found a way to cross that barrier. 
 
“Once a person is infected with HIV, it can take as little as eight days for the virus to find its way into the brain where it targets subcortical structures called the basal ganglia,” said Courtney. "The basal ganglia have a strong connection with the frontal lobe of the brain, creating what we refer to as the frontostriatal circuit. Damage to this circuit has been associated with impaired memory, attention, and processing speed. Even while taking antiretroviral medications, over time nearly half of HIV-infected adults will begin to experience cognitive symptoms that are indicative of frontostriatal dysfunction, known as HIV-associated neurocognitive disorder or HAND. For the great majority of HAND patients, the impairment is mild, but a small minority develop full blown dementia.
 
Courtney has explored this dysfunction by evaluating HIV patients with a series of neuropsychological tests and MRIs to evaluate the impact of HIV throughout the brain. Her research subjects were asked to perform a battery of neuropsychological tests that assess verbal fluency, working memory, mental flexibility, response inhibition, and motor speed. Courtney had Burzillo’s students complete similar assessments during her visit. In one test of working memory she asked students to listen to series of numbers and then write them down. The test progressed from groups of four numbers to groups of nine numbers.
 
“It is typical for a human to be able to hold seven numbers +/- two in their working memory.  This test is very challenging for people in the later stages of HAND,” she commented. Some students were then asked to complete a mental flexibility test. The Wisconsin Card Sorting Test was created to test “set-shifting” in a clinical setting. It is very similar to the card game UNO, so Courtney brought along her children’s set of cards from home.
 
“How flexible are you? Can you change your strategy when the colors, numbers, or symbols on the card change? It can be very challenging for people in the later stages of HAND to make these changes, particularly when speed is involved,” said Courtney. "People with mental flexibility have little trouble in responding to changes in color or number on cards that are turned over in this test and the students completed the task with ease."
 
In addition to administering neuropsychological tests to her subjects, Courtney also gathers data from MRIs of her subjects’ brains. This allows her to study the physical changes in the regions of the brain associated with the types of impairment seen in patients with HAND. Courtney described to students how MRI technology works, and how it allows neuroscientists to track changes in the thickness of gray matter and integrity of white matter tracts in the brain. Both are important to proper brain function: gray matter is associated with processing and cognition, and white matter helps coordinate communication between different brain regions. Using structural MRI, Courtney has revealed regions of both degeneration and swelling in the gray matter of HIV patients, prior to any signs of cognitive impairment. Applying diffusion tensor imaging (DTI), ideal for investigating whiter matter tracts, to the same cognitively asymptomatic HIV patients, she has identified underlying white matter areas where the tracts have become compromised. By analyzing MRI films in conjunction with neuropsychological tests, it is clear that the structural brain changes occur before subjects show signs of cognitive illness. 
 
Courtney’s leave of absence has enabled her to complete what has been a 14-year time commitment to her graduate studies, juggling the demands of full-time teaching at Rivers and raising a family. During her years at Rivers, she has felt the impact of her own studies on her teaching style, both in the inquiry-based curriculum she has developed in her Biology and Chemistry and AP Biology classes, as well as in the Neuroanatomy and Behavior elective she has taught.
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