Archive for the ‘HSMBB Events’ Category

Interdisciplinary projects from five MBB postdocs

Monday, November 30th, 2009

As undergraduates, we might be accustomed to visiting departmental websites to learn about faculty research. Last Monday’s MBB Postdoctoral Fellows event showcased five postdocs who have struck out on their own, working on research projects that cross interdisciplinary boundaries. Fiery Cushman, Mark Eldalef, Andrea Heberlein, Adam Kampff, and Brian Russ are each sponsored by at least two different MBB departments in their studies of moral judgments, decision-making, mood, learning, and default networks.

Fiery Cushman, jointly sponsored by Joshua Greene (FAS/Psychology), Martin Nowak (Program Evolutionary Dynamics), and David Laibson (FAS/Economics), is puzzling out the different weights we assign to outcomes and intentions in moral judgment and punishment. Surprisingly, a dice game experiment revealed that even when chance, rather than a partner’s choice, influenced how much money someone received, the person often chose to reward or punish on the basis of the outcome. Cushman hypothesizes that we punish outcomes because outcome-based learning is a better teaching strategy. This was corroborated by a dart experiment in which subjects learned the difference between colors that lost and earned money for their partner more quickly when their partners rewarded and punished based on outcome. Cushman believes that an outcome-based attitude towards punishment evolved when we did not have the language to explain intent, and that we should be critical of our own moral psychology and give each other more information so that intent is easier to judge and accidents can be distinguished from maliciousness.

Mark Eldalef, sponsored by Alvaro Pascual-Leone (HMS/Neurology) and Randy Buckner (FAS/Psychology) does work on changing default network activity with Transcranial Magnetic Stimulation (TMS). The default network is the nexus of brain areas active when the brain is awake but resting, not focused on tasks in the outside world. Its activity is anti-correlated with the visual attention network, and it has been implicated in introspective thinking, considering the future, and putting oneself into other people’s mindsets. The default network is often aberrant in disease states such as Alzheimer’s as well as in normal aging. Eldalef’s work aims to find whether TMS can change connectivity within the default network, whether the signal is propagated throughout, if the opposite effect might be found in non-stimulated hubs, and if the result might be distance-dependent. He found that 20hz TMS pulses to the inferior parietal lobule increase default network activation while 1hz pulses decrease it, and that this effect is time-dependent, apparent right after TMS but less visible later on due to compensation. His work demonstrates that we can directly manipulate resting networks in the brain, rather than through behavioral studies, and may have implications for further research on the default network’s function, its reactions to stress, and possibilities for altering disease courses.

Andrea Heberlein, sponsored by Daniel Wegner (FAS/Psychology) and Moshe Bar (HMS/Martinos), is interested in using behavioral and neuroimaging studies to learn how context, motivation and mood influence our perceptions of other people’s minds. Normal research subjects interpret a movie containing geometrical characters behaving in seemingly intentional ways by anthropomorphizing them. Evolutionarily, we tend to err on the side of over-attributing minds to objects because it is the safer route. The content we attribute to other minds tends to fall into two categories, experience (phenomenology) and agency (planning/control). Emotions such as sadness seem to increase our perceptions of others’ experience, increasing our empathy and decreasing our propensity to stereotype. Frustration, on the other hand, causes us to attribute excessive blame and agency to other minds, while dampening our perception of their experience and ability to be affected by our actions. Her next steps will involve using MRIs to detect what other moods are associated with which types of information about other minds, for instance, whether her predictions that fear causes a perception of increased agency but no change in experience, and embarrassment a perception of more agency and experience, are supported by brain scans.

Adam Kampff, sponsored by Bence Olveczky (FAS/Organismic and Evolutionary Biology) and Florian Engert (FAS/Molecular and Cellular Biology) is using rodents as a model for motor and procedural learning. He tests rats’ learning in the absence of adaptive behavior by teaching them a highly stereotyped motor skill involving pressing levers at specific time intervals. Although rats’ actions look unplanned and unskilled, slowing down and comparing several videos of a rat who has been practicing this motor task for weeks shows that they have learned a precise procedure, down to the exact timing and placement of each toe. Kampff is also interested in how this motor memory is stored, a question which is addressed by lesions studies, transient chemical inactivation, and optical excitation and inhibition of specific brain regions. Kampff found that removing the motor cortex of a rat that has already learned the procedure has no impact on performance. Optical imaging has been an obstacle in awake, behaving rats, but the Olveczky lab has found a way of combining water rewards and head mounting to use powerful imaging tools to examine the pattern of neural activation in conscious, active rats.

Brian Russ, sponsored by Alvaro Pascual-Leone (HMS/Neurology) and Marc Hauser (FAS/Psychology), studies the neural basis of moral cognition and the cognitive and evolutionary components of recognizing ownership. Moral decision-making derives from three different areas: the right temporal parietal junction (rTPJ), the dorsalateral prefrontal cortex (DLPC), and the medial prefrontal cortex. Russ is currently using transcranial magnetic stimulation (TMS) to study the role of the DLPC. So far, using TMS to stimulate the DLPC has caused subjects to perceive personal harms as more forbidden than under control conditions, and is particularly sensitive to using people as means. Russ also does field work on ownership in the minds of animals and has discovered that rhesus monkeys that are offered two identical rewards will go for the one that is less connected to the research (e.g. not tied by a rope), as the attachment makes the reward seem more competitive. This suggests that they have some understanding of ownership in the case of a direct physical connection, but further work remains on how rhesus monkeys perform on tasks of nonexplicit ownership.

Social networks

Wednesday, November 18th, 2009

Medical sociologist Nicholas Christakis gave the keynote speech at the recent Harvard Undergraduate Research Symposium regarding his research on social networks. His talk surveyed the various studies he has conducted, all of which point to the same essential finding: that a slew of behaviors and characteristics, including smoking, obesity, happiness, and even movie preference, can be transmitted from person to person in a social network. This means that your likelihood of smoking, for instance, is not only higher if your friend smokes, but also if his friends smoke, and also if their friends smoke.

This "Three Degrees Rule,” as Christakis puts it in his recent book Connected, holds for other behaviors. For instance, according to one of Christakis’ studies, happiness and sadness can be transmitted quickly and noticeably in a college dorm, where one’s likelihood to be happy depends on how many people, within three degrees of influence, are also happy. For another example, Christakis found that people who identified Pulp Fiction as a favorite movie on Facebook were far more likely to be friends with others who identified it as their favorite movie, but exhibited almost no overlap with the network of those whose favorite film was Love Actually.

Christakis’ research suggests that certain health and social phenomena are, at least metaphorically, epidemic. I asked him after the conference what he thought the "pathogen” might be—that is, by what mechanism do such influences spread?  Though he hasn’t specifically researched that question, he believes it largely has to do with the transmission of norms. Seeing your friend smoke alters how acceptable you find smoking, thereby changing your attitude towards the smoking behaviors of your other friends. Christakis admitted there might be other mechanisms as well—for instance, transmission of the actual behavior, or differential patterns of genetic susceptibility.

Nicholas Christakis, MD, PhD, MPH, is Professor of Medical Sociology and of Medicine at Harvard Medical School, and Professor of Sociology in the Harvard Faculty of Arts and Sciences. He is also master of Pforzheimer House.

Fighting fire with fire

Tuesday, November 17th, 2009

Well that's what Nworah Ayogu, a Senior concentrating in Neurobiology, is doing in the Rabkin Lab at the Massachusetts General Hospital.  Targeting brain tumors with viruses may seem like something out of a science fiction movie, but Ayogu has been working to use mutant viruses to trigger the immune response against cancer cells, in what is called tumor vaccination.  One type of primary brain tumors in the central nervous system, known as gliomas, is extremely malignant, with a median survival time of twelve to fifteen months.  Researchers have been studying two particular types of treatments in an attempt to combat this deadly disease.  One, known as immunotherapy, attempts to elicit an immune response against tumor cells, while the other, which uses oncolytic herpes viruses, is what Ayogu is especially interested in.  These herpes implex viruses (HSV), modified so that they will only replicate in tumor cells, are dependent for replication on certain factors only seen in rapidly proliferating cancer cells.  HSV replication in the body normally triggers an immune response, which we more commonly recognize as either cold sores or genital Herpes, so when the HSV in tumor cells replicate and lyze, it is proposed that an anti-tumor response will be generated indirectly.  Using the HSV strain G47delta, Ayogu has established a mouse model to study whether G47delta can activate the dendritic cell response. He found that the dendritic cells matured after exposure to virally-infected tumor cells, indicating that tumor vaccination had been achieved in the mice studied.  Ayogu admits that there is still work to be done and is currently furthering this line of research as we speak.  I, for one, would love to see this succeed.  Not only would break-throughs in this field help to combat brain tumors, but it would also be incredibly cool to fight cancer with mutant viruses.

Ayogu presented this work, entitled "Establishment of a Gliomal Model for Tumor Vaccination Using Virally Infected Tumor Cells,"
at the Harvard Undergraduate Research Symposium (HURS) this past weekend.

Janet