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March 05, 2005— Ottawa, Ontario

"Is he in there?" That was the question posed by the grief-stricken and frustrated mother of a son involved in a serious car accident. Although the son was seemingly unresponsive to all possible stimuli, the mother nevertheless felt her son was in fact "in there" and was determined to prove it.

Photo montage of a woman's head and her brain

According to Dr. Ryan D'Arcy, researcher with the NRC Institute for Biodiagnostics – Atlantic, questions about the extent of brain injury and brain function play a major role in choosing the right therapy for people with brain injuries. "Establishing that such persons are capable of brain functions means that certain therapies can be considered," D'Arcy notes. He adds that it is as simple as ensuring that these patients, who are capable of stimulation, are not excluded from watching television. On a more serious note, it also forces changes in behaviour among treatment staff because patients cannot and should not be referred to as lacking function, as in "He/she can't understand you."

D'Arcy made his comments as part of the Mind in Matter seminar series held by NRC. D'Arcy's presentation and another talk by Dr. Jagdeep Sandhu of the NRC Institute for Biological Sciences underlined important work being done in the research community to understand behaviour and cognition in terms of psychology as well as physiology and very real physical changes that occur in the brain. As researchers on both sides would probably admit, historically, there has been a noticeable philosophical divide separating mind from matter. However, more recently, the push is on to unify thinking this area.

As part of her talk, Sandhu, for example, highlighted work being done to understand cellular-level changes that take place in patients suffering from neurogenerative disorders such as Parkinson's disease. One of the strategies being explored by the team involves using gene-based therapies to help affected cells to better resist changes brought on by the disease. Such therapies first require a firm understanding of the complexity and the magnitude of genetic changes that take place in response to a disease. The objective is to find an important function that can, essentially, be disrupted or targeted to behave in another way.

How fMRI Works

The blood oxygen level dependent (BOLD) fMRI technique takes advantage of the fact that the oxygenation state of hemoglobin affects its magnetic properties. Brain regions that are active require more oxygen. Oxygen is delivered by increasing the blood flow to these active brain regions. Scientists compare the differences in blood flow between a resting condition and an active condition to find regions that are associated with one task and not the other. They are then able to detect these differences with MRI because there is a difference in the magnetization properties of oxygenated and deoxygenated blood. These functional images are very powerful means by which neuroscientists gain insight into the working brain.

D'Arcy approaches the problem from a different perspective, in this case, starting with a detailed understanding of brain physiology and functions. Perhaps geography is a better term to describe this work because, using techniques such as functional magnetic resonance imaging (fMRI), researchers have actually been able to see brain activity in real time and identify the exact location of this activity in the brain. This is critically important since it allows doctors to see what parts of the brain are still receiving blood and oxygen and makes sure that extra healthy tissue is not removed during brain surgeries.

D'Arcy, who works as part of the Brain Repair Centre in Halifax, Nova Scotia, uses fMRI on its own but often with another tool used by neuroscientists, the EEG (electroencephalography), which captures information about brain waves. Different cognitive functions look different in terms of waveform characteristics.

Left panel: Photomicrographs of cultured astrocytes (stained red) and neurons (stained green). Right panel: Photomicrographs of characteristic neuropathology of Parkinson's disease. Dopamine neurons immunostained with antibody to tyrosine hydroxylase and two lewy bodies immunostained with antibody to ubiquitin (stained brown)
Left panel: Photomicrographs of cultured astrocytes (stained red) and neurons (stained green). Right panel: Photomicrographs of characteristic neuropathology of Parkinson's disease. Dopamine neurons immunostained with antibody to tyrosine hydroxylase and two lewy bodies immunostained with antibody to ubiquitin (stained brown)

For example, one test presents pieces of information that are clearly incongruous, such as showing several pictures of common objects (e.g. a picture of a ball) and then pairing them with incongruent descriptions (e.g. hearing the word "car"). The experiment creates a very distinctive waveform, known as the N400. When D'Arcy and his colleagues were faced with the question of "Is he in there?" they used this experiment that, to both surprise and relief, generated the N400 response and provided a definitive yes to this important question.

D'Arcy is also applying fMRI to similar clinical assessment problems in surgical planning. Testing with fMRI prior to surgery can confirm that brain regions in question are intact and clearly capable of supporting important cognitive functions; important experiments providing critical and hopeful news to patients and those who care for them.

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