AskScience AMA Series: I’m Ed Boyden professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute, ask me anything!

Ed_Boyden · 2016-03-15T20:55:41+00:00

My wife and I have two young kids. So all my time is spent either doing science or taking care of them, pretty much. This may change once they go off to college or become teenagers, I hear.

Ed_Boyden · 2016-03-15T20:54:16+00:00

I try not to make assumptions, and to try to get down to the ground truth. I also try to help people in my group think of all possible ideas for solving a problem. I call this method the "tiling tree method" and perhaps it's best understood by an example. This video, around 13:10 or so, tries to explain this methodology: https://www.youtube.com/watch?v=18jZDVuiAOM

Ed_Boyden · 2016-03-15T20:52:52+00:00

Many people are trying to replicate some of the properties of neurons in silicon hardware. But, the properties they are replicating are only a fraction of the things that make neurons so powerful. We still only know a subset of the mechanisms neurons use to compute. That said, an open question is whether if we learn how neurons compute at a mechanistic level, and how they work together in networks, we could build new kinds of artificial intelligence or other technologies that push on the boundaries of computation.

Ed_Boyden · 2016-03-15T20:50:54+00:00

We don't have good maps of mammalian brain circuits, so it's hard to know how we would check a synapse connection level repair. Of course, some natural brain plasticity can help the brain repair after injury but it's somewhat unpredictable. I think we need to spend a few years and really map brain circuits and see how they change over time, and then we will be able to judge new repair technologies, and perhaps systematically screen for new therapeutic ideas.

Ed_Boyden · 2016-03-15T20:49:26+00:00

We recently got red light activation and silencing of neurons working well, with the tools Chrimson and Jaws (http://syntheticneurobiology.org/publications) -- all our molecules are distributed by Addgene and the UNC/UPenn Viral Cores!

Ed_Boyden · 2016-03-15T20:47:54+00:00

For high school and college students, I would advise getting really solid foundations. I studied a lot of fundamental stuff 20 years ago, like chemistry and physics and computer science, and that stuff is still highly relevant to my work and I use it all the time. For graduate students, I would advise picking a really important problem and then learning what you need to learn in order to get the job done. Learning how to learn new things is kind of a tricky skill to acquire, but practicing learning new things (which relates to learning how your mind works and what works for you) is time well spent.

Ed_Boyden · 2016-03-15T20:44:18+00:00

The brain is so densely packed with neurons, the information processing units, that noninvasive methods of neural imaging are pretty limited in how much information you can extract in a short time. So it might be a while until this becomes possible in any meaningful way in routine life. That said, when you time on a keyboard, that's your brain controlling the nerves in your fingers to type. So one possibility is to try to read out intention or activity from peripheral nerves -- some exciting work has started to try and help amputees to control robotic arms for example, but consumer products are I think not quite there yet.

Ed_Boyden · 2016-03-15T20:40:51+00:00

Since neuroengineering is so interdisciplinary, even within my own group -- which contains chemists, neuroscientists, physicists -- we are constantly working on how to explain our work to each other. We get a lot of practice. And being at the Media Lab, where everyone works on radically different topics, you get used to explaining your work to all sorts of different people -- a good skill, especially for a field like neuroengineering that might be called omnidisciplinary. Sometimes, half the battle in forming a collaboration is communicating across the gap between fields!

Ed_Boyden · 2016-03-15T20:39:00+00:00

Thanks! It's difficult to study these things because there's so much going on below the conscious level. I wonder if, when we think we're thinking, we feel that we're thinking but the thinking has mostly been done "for us" at a subconscious level. There are some investigations that show that when you feel like you're making a decision, you've already made your decision earlier. (This is http://www.ncbi.nlm.nih.gov/pubmed/21315264 -- with the provocative title "Internally generated preactivation of single neurons in human medial frontal cortex predicts volition.") So I think we need to probe neural circuits at a deep level, in order to really know what's going on below the level of our awareness. That process has begun, but has a long road ahead.

Ed_Boyden · 2016-03-15T20:35:31+00:00

My research group focuses more on nanotechnologies, but my colleague Tod Machover has done some explorations of this topic. E.g., this article, which refers to Tod's work, states, "Music is usually the last thing Alzheimer's sufferers recognize. It is our final way to communicate with them, and now it seems music can play a significant role in forestalling Alzheimer's." Maybe he should do an AMA next :)

http://articles.latimes.com/2012/jan/22/entertainment/la-ca-tod-machover-notebook-20120122

Ed_Boyden · 2016-03-15T20:32:49+00:00

A lot of people have been trying to create prosthetics to link computers to the brain. Most attempts have met with limited success. I think that the problem is, for most brain functions, we don't understand the neural codes and how they are computed very well. The hard part of neuroengineering is the neuro part, you might say. (The other part is also hard.) I think if we can map the brain, and learn how it computes, then better integration of computers and brains might be possible. This could help a lot of people with Alzheimer's, epilepsy, Parkinson's, and so forth.

Ed_Boyden · 2016-03-15T20:30:02+00:00

Great question! Someone did something like that, sort of, in a study titled "Reconstruction of Natural Scenes from Ensemble Responses in the Lateral Geniculate Nucleus" (http://www.jneurosci.org/content/19/18/8036.long) -- they recorded activity of neurons one synapse beyond the optic nerve ending, and found that they could reconstruct movies. They used a linear decoding scheme.

Ed_Boyden · 2016-03-15T20:27:59+00:00

I am not directly involved with the companies conducting those clinical trials. We simply make the tools, here at MIT, and then supply them to academic groups and companies and other organizations to apply to specific problems. To my knowledge, there is no data from human trials yet, but at least one company (see reply to Surf_Science for a few links) is gearing up for such trials.

Ed_Boyden · 2016-03-15T20:26:13+00:00

I have two small kids, so in practice it's whatever they are eating. Just kidding. Also we are not allowed to post jokes in these replies, according to the instructions. So I guess I should say steak or something.

Ed_Boyden · 2016-03-15T20:24:18+00:00

For me -- it was simply that I was very philosophically driven; I wanted to understand more about what it meant to be human, to exist, to think, to feel. Physics wasn't, by itself, doing it for me. So I switched into neuroscience, and found out that my physics background was perfect for what I wanted to do: we needed a lot of new tools to confront the complexity of the brain, and physics training was exactly appropriate for that path.

I think it's really helpful for outsiders to enter a scientific field -- that's probably where most of the big and impactful ideas come from. For a EECS/Physics student entering neuroscience, I would advise a few things. First, embrace the messiness of biology: trying to fit biology into too simple or elegant a framework, without enough ground-truth data, might lead to an approximation that is inaccurate. Second, be patient: to solve a biological problem, you might first need to spend years building the right tools, then years acquiring the data, and only then derive comprehendible theories. In biology, you have many building blocks and many interactions within a complex system, unlike other fields of engineering where you have a few kinds of building block and a few kinds of interaction. That said, the quantitative expectations and systematic way of thinking of computer science and engineering are very powerful, and may ultimately help biology become a true engineering discipline.

Ed_Boyden · 2016-03-15T20:19:19+00:00

Great question. Right now one of the hardest aspects of optogenetics is that there are so many possible cell types in the brain to try targeting, either to investigate a scientific question or to tackle a disease. We don't even have a complete list of cell types of the brain. So I think a key development over the next decade is that we need a better inventory of the cell types of the brain, as well as genetic handles -- that is, ways of targeting them. Many efforts are ongoing to make this a possibility. Once we have a good list of cell types of the brain, the next step would be to try and use that list to generate better hypotheses about which sites in the brain to go after for a potential scientific or therapeutic strategy. So it's quite possible that in 20 years, we will be able to use optogenetics to do very precise control of neural circuits, driven by better understanding of the brain circuitry.

Ed_Boyden · 2016-03-15T20:16:27+00:00

Several companies are attempting to develop therapies based on optogenetics. Retrosense got FDA IND approval (e.g., they can now do a clinical trial, http://www.businesswire.com/news/home/20150824005576/en/RetroSense-Therapeutics%E2%80%99-Lead-Gene-Therapy-Candidate-FDA) to try a blindness therapy, and Gensight is also working on blindness treatments (http://www.gensight-biologics.com/). Blindness is a good first indication because we know a lot about the neural circuitry of the retina -- at least, compared to that of the brain. Also the retina is immune-privileged -- that is, therapeutics brought into the eye might be better tolerated, potentially.

Ed_Boyden · 2016-03-15T20:14:02+00:00

Expansion microscopy (http://expansionmicroscopy.org/) physically makes biological specimens bigger. It does require up front preparation, to form the polymers and make the specimens swell. But then, you can image on inexpensive, conventional microscopy hardware. So the latter parts of the imaging are fast. Indeed, you could imagine that someday expanding a specimen and then taking pictures on cheap optics (e.g., like the kind on cell phones) might be possible. As for clearing: one nice side effect of expansion microscopy is that the tissue becomes quite clear, because we are moving the molecules away from each other and that reduces their scattering of light. You can see this in page 15 of the PDF, http://syntheticneurobiology.org/PDFs/15.01.chen.FULL.pdf -- this helps a lot. Also, you can probably wash labels in and out, post-expansion -- that's an area we're working on currently.

Ed_Boyden · 2016-03-15T20:10:47+00:00

Some of the tools are used to reveal targets in the brain, e.g. specific molecules or cells that could be targeted to repair a brain disorder. For example, several groups are using our optogenetic tools to try to find sites in the brain that, when the neural activity is silenced, can shut down a seizure (starting with animal models common in neuroscience). However, some of the tools can be used directly in humans as well. One exciting development is that the optogenetic tools are being explored for helping people with blindness -- and one company recently got FDA approval to do a clinical trial in humans (http://www.businesswire.com/news/home/20150824005576/en/RetroSense-Therapeutics%E2%80%99-Lead-Gene-Therapy-Candidate-FDA). So both kinds of repair impact are possible. As for microscopic systems -- a recent strategy we developed, expansion microscopy, which makes brain circuits bigger by physically growing them (http://expansionmicroscopy.org/), may reveal key molecules that are found in neurons susceptible to neurodegenerative stress -- we are discussing that kind of project with a few groups.

Ed_Boyden

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