Focusing on recent experiments with monkeys, Dr. Michael Shadlen, physiology and biophysics, University of Washington, spoke to students and faculty at the Biotechnology Building about deciphering neural codes of activity yesterday as part of the Department of Neurobiology and Behavior’s weekly seminar series.
Prof. Joe Fetcho, neurobiology and behavior, introduced Shadlen and kicked off the lecture by explaining that Shadlen would focus on a “fundamental question in neuroscience.”
“You saw the poster about the lecture, and then you processed that info in your head and acted upon a decision to come here. Michael studies everything that happens in [your brain] between seeing that poster and coming to the talk,” Fetcho said.
Shadlen began his speech with an overview of the decision making process, giving an example of factors that influenced President George W. Bush’s decision making process to enter Iraq. He showed a number of different pictures, including an oil pump, a magic 8-ball, and Bush’s father, 41st President George H.W. Bush.
“He had a number of possible decisions to make [when entering the war], motivated by a number of different factors. We might view some of these as unethical, but he followed the decision-making process,” Shadlen said.
Shadlen then introduced the core experiment that he would base the rest of his lecture upon. A monkey, placed in front of a monitor, is tested to see how it decides the net direction of motion from one dot to another, to either the left or right side of the screen. The experimenter can alter a number of variables including the fraction of moving dots and the motion strength.
Shadlen focused on two parts of the monkey’s brain, the lateral intra-parietal cortex (LIP) and the middle-temporal area (MT), both of which contain two distinct types of neurons and influence choices. When the monkey looked in a “preferred” direction, the sound of MT neurons cascading in the brain could be clearly heard, but when the monkeys looked in a “null” direction, no sound could be heard.
“Neurons take info and convert it to some plan of action,” Shadlen said.
Milliseconds before the monkey looked in a certain direction, neurons gathered evidence as to the benefits of looking in a certain direction. Once enough evidence was acquired to break a directional bound, the monkey looked in a certain direction.
Shadlen introduced the “diffusion-to-bound” model to illustrate this evidence gathering process.
After a quick build-up of neurons, there is suddenly a drop which Shadlen termed the “resetting neural integrator,” which he hypothesized was the brain clearing itself of previous memories to obtain new evidence. Evidence continues to accumulate in one direction until the monkey finally looks.
“This spatial selectivity holds the seeds to understanding higher brain function in everyday situations and functions,” he said.
Shadlen continued his speech by discussing MT microstimulation experiments, which stimulate certain neurons in the monkey’s brain to get the monkey to look in a certain direction. However, even when certain neurons were stimulated, the monkey would look in the opposite direction than expected.
“The monkey decided to look in the left direction, even when we stimulated the right neurons. However, the right neurons slowed down this process considerably, so that the monkey’s reaction time was slower than usual. Microstimulation has a small effect on choice, but a large effect on reaction time,” Shadlen said, claiming an identical paradigm was observed in the LIP neurons as well.
Shadlen also introduced a number of unanswered questions on how the integral is computed, how the directional bound is set, and how a bound crossing is detected.
“There are many things we don’t yet understand, and many of my statements I’ve made today are still preliminary. Still, this research will have many applied functions in the future,” he said.
Shadlen ended his lecture with a hypothesis that many disorders of higher brain functions might be caused by certain neurons’ inability to integrate and gather evidence, a “leaky neural integrator.” This lack of evidence would lead to a state of perpetual confusion.
“When I was in residency, many times I would see patients administered on an overdose of PCP. Drugs like these interfere with the evidence-gathering process and render the subject bewildered. You could always spot these patients, even from all the way across the emergency room, because of the look of utter confusion on their faces,” Shadlen said.
Students had a mixed reaction to the lecture, with many stating it was too confusing.
“I guess it was interesting, but most of it just went over my head,” Andrea Knezevic ’08 said.
Shadlen has been at the University of Washington since 1995, and was appointed a professor this year. He is a new investigator in medicine at the Howard Hughes Medical Research Institute, and is the recipient of many awards, including the McKnight Scholars Award, the Sandoz Award, and the Dana Fellowship.
Archived article by William Cohen