Grant: Operating Grant

Multiple sclerosis (MS) is the most common neurological disease affecting young adults in Canada. MS can cause symptoms such as poor thinking and memory, poor use of the arm and hand, and reduced walking ability. Techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) provide insight into changes in the brain caused by MS. Yet surprisingly, the severity of these symptoms is hard to predict by looking at images of the effects of MS on the brain. It seems that the brain has mechanisms that allow people to compensate for damage caused by MS. Our research team is studying a mechanism that could explain why some people have preserved motor and cognitive abilities even though their brain has been affected by MS. We know that activity levels in the brain are determined by a combination of excitatory activity and inhibitory activity in nerve cells. Using TMS, we found less inhibitory activity in the brains of MS patients with good cognitive functioning. We are proposing a series of studies with the goal of understanding this possible mechanism by which people with MS might achieve better functioning. First, we will test whether the inhibitory levels in the brains of people with MS are abnormal compared to people with healthy brains. This may provide clues about what causes changes in brain inhibition. Next we will use MRI to examine whether the beneficial effect of low inhibition depends on the amount and location of MS damage in the brain. Finally, we will use a novel method called magnetic resonance spectroscopy to test for abnormal levels of a chemical called GABA that is an important regulator of inhibition in the brain. We expect the results will help us understand better how the brain responds to disease, not only in MS but also in other neurological disorders. They may also point the way to new therapies to help people with MS achieve their highest possible level of functioning.