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DMS SYMPOSIUM Speakers Probe Normal and Diseased BrainWe have all experienced perceptual tricks and visual illusions--the image of a vase that suddenly transforms into the space between two faces in profile, or a seemingly random field of black spots that resolves itself into the image of a Dalmatian. The visual stimulus we receive remains the same, but somehow from one moment to the next we see it as something different.
John Assad wants to figure out how the brain makes meaning out of what it sees. (Photo by Graham Ramsay) "The brain is not a passive filter," said John Assad, HMS assistant professor of neurobiology, speaking on June 5 at the Division of Medical Sciences-sponsored Alumni Symposium on Neurosciences. Rather, the brain takes an active role in making sense of incoming information, and Assad has been working to pinpoint where in the brain these leaps of judgment are made. The structure of the brain suggests this process is a hierarchical one: retinal neurons simply register stimuli, but as this information is passed further along, some information is filtered out and an understanding of what is seen emerges. Seeing, Not Necessarily BelievingAssad's team works with macaque monkeys that are trained to perform certain tasks in response to visual stimuli, while electrodes record the activity of specific neurons. For example, certain neurons in the visual system are keyed to specific directions of movement. Assad and his colleagues showed columns of dots that would shift to the right or left, sometimes smoothly and sometimes more ambiguously. The monkeys recorded what they believed to be the direction of movement, and their choices were compared to the actual firing of direction-specific neurons in three regions of the brain involved in different stages of visual processing. The team found that in the lateral intraparietal area (LIP), a downstream component of the brain's visual-processing system, the firing of the neurons more closely matched what the monkeys thought they saw--as opposed to the more upstream neurons in the middle temporal region, which registered the true direction of movement. "The neurons in LIP prefer what the monkey is perceiving instead of the physical stimulus," Assad said, suggesting that somewhere along this path the brain is reinterpreting what it sees.Unmasking Brain DisordersThe other presenters at the symposium addressed some of the current hypotheses in neurodegenerative diseases like Alzheimer's and Parkinson's. Carmela Abraham, DMS '89, professor of biochemistry at Boston University School of Medicine, outlined a history of discoveries about amyloid-beta, the aggregating protein in Alzheimer's disease.One of the most intriguing ideas that has surfaced along these lines is that many neurological diseases--Alzheimer's, Parkinson's, Huntington's, and other polyglutamine disorders--arise from surprisingly similar processes of protein malformation and aggregation, leading some to hypothesize that they may be essentially the same disease with a shared pathway. Mel Feany's lab at HMS has taken advantage of fruit fly models of neurodegenerative disease, which now allow the researchers to test genetic theories more rapidly than in mouse models. An assistant professor of pathology at Brigham and Women's Hospital and a 1993 graduate of DMS, Feany used a fly model for Parkinson's and tauopathy that her team had developed, as well as polyglutamine models, to compare one disease with another in search of common genetic pathways that result in protein abnormalities. So far, despite the compelling notion of a singular mechanism, the researchers have found little commonality. "The pathways are surprisingly distinct," Feany said, which would suggest that therapies need to target an individual disease rather than a common mechanism in all neurodegeneration. --Courtney Humphries |
