RIP Roger Tsien, 1952-2016

2016_08_31_tsien_roger

Sad news today – Roger Tsien passed away one week ago.

Can anyone imagine biology today without GFP? And though he is best known for that – he did share the Nobel prize for GFP, after all – Roger Tsien did much more. One of my favorite stories about Roger (and he was a character; you couldn’t be at UCSD without one or two Roger stories) came from a talk he gave while I was there. He was asked to step in at a somewhat late moment to give a series of three one-hour lectures on his life’s work. It was one of the best talks I have attended, clear and insightful and packed with interesting anecdotes.

He begun describing his struggles as a graduate student, how he had a hard time doing electrophysiology. His solution? He created BAPTA, the calcium chelator that is the basis for neural imaging. Yeah: electrophysiology too hard? Just create the basis for calcium imaging. Much easier. (And he was quite honest; it was much easier for him.)

You should of course read that original BAPTA paper (this is under-appreciated!). Then of course there is his GFP paper, establishing a point mutation with much improved characteristics. Here is his Nobel lecture. I don’t think it’s an understatement to say that these are just the tip of the iceberg.

Monday Open Question: Does anyone actually know what a ‘reflex’ is?

It has been a while since I have done one of these…

As I was working on a fellowship application last week, I realized that I did not know whether what I was studying would count as a ‘reflex’ or not. What was the definition?  Is something not a reflex simply when we have a hard time mapping the input to the output? The canonical reflex arc kind of gives us one definition, but a good definition will be general – applicable to both mammals and non-mammalian creatures (dragonflies, antlions, worms). I asked on twitter and got some unsatisfying answers.

Is everything that is fewer than n synapses a reflex? What if those connections are mediated by state in some way (say, a peptide) so that some mapping from sensation to action depends on hunger, on mood, on whatever else? Are the only actions that are not reflexes those that are not dictated by sensory input…somehow? Is this just a lazy way to beat up on invertebrate neuroscientists?

Papers for the week, 8/21 edition

Coordinating long-latency stretch responses across the shoulder, elbow and wrist during goal-directed reaching. Jeffrey Weiler, James Saravanamuttu, Paul L Gribble, J. Andrew Pruszynski.

Internal states drive nutrient homeostasis by modulating exploration-exploitation trade-off. Veronica Maria Corrales-Carvajal, Aldo A Faisal, Carlos Ribeiro.

Automatic Neuron Detection in Calcium Imaging Data Using Convolutional Networks. Noah J. Apthorpe, Alexander J. Riordan, Rob E. Aguilar, Jan Homann, Yi Gu, David W. Tank, H. Sebastian Seung.

Wake-sleep transition as a noisy bifurcation. Dong-Ping Yang, Lauren McKenzie-Sell, Angela Karanjai, and P. A. Robinson.

Rationalizing spatial exploration patterns of wild animals and humans through a temporal discounting framework. Vijay Mohan, K. Namboodiria, Joshua M. Levy, Stefan Mihalas, David W. Sims, and Marshall G. Hussain Shuler.

Optimality of Spatially Inhomogeneous Search Strategies. Karsten Schwarz, Yannick Schröder, Bin Qu, Markus Hoth, and Heiko Rieger.

Massively Parallel Interrogation of the Effects of Gene Expression Levels on Fitness. Leeat Keren, Jean Hausser, Maya Lotan-Pompan, Ilya Vainberg Slutskin, Hadas Alisar, Sivan Kaminski, Adina Weinberger, Uri Alon, Ron Milo, Eran Segal.

Loom-Sensitive Neurons Link Computation to Action in the Drosophila Visual System. Saskia E.J. de Vries, Thomas R. Clandinin.

A spike-timing mechanism for action selection. Catherine R von Reyn, Patrick Breads, Martin Y Peek, Grace Zhiyu Zheng, W Ryan Williamson, Alyson L Yee, Anthony Leonardo & Gwyneth M Card.

Automatic Segmentation of Drosophila Neural Compartments Using GAL4 Expression Data Reveals Novel Visual Pathways. Karin Panser, Laszlo Tirian, Florian Schulze, Santiago Villalba, Gregory S.X.E. Jefferis, Katja Bühler, Andrew D. Straw.

Unrelated to all that, 8/20 edition

Will somebody please give Norm Macdonald another TV show? And why it’s partly his own fault. If you don’t like the moth joke, I don’t understand you.

The Irritating Gentleman (1874). By Berthold Woltze

TheIrritatingGentleman

The Heiman Lab turned their website into a text adventure. This is seriously amazing, though I’m a little upset it won’t let me eat the petri dish.

You will be able to order a self-driving Uber in Pittsburgh this month. Though obviously there will be someone sitting in the driver’s seat for safety reasons. Maybe the ride is free if you get in an accident?

Someone recorded their heart rate during a conference talk. Fear is the mind killer:heartrateduringtalk

When are babies born?

whenarebabiesborn

The Broad has spent $10 million this year and $5 million last year on the CRISPR dispute. Now we hear that a grad student claims he was working on CRISPR in the Zhang lab but the lab only really jumped on the work after seeing Doudna’s in vitro paper. The Broad says he was lying to get a job with Doudna and stay in the country.

Is it story that makes us read? Maybe not, but this essay has one of the worst defenses of its theses that I’ve seen in a while.

If you are a neuroscientist and want to see educated laypeople try to puzzle out  neuroscience by logic and anecdotes (unsuccessfully), try reading this post and its comment thread.

Papers for the week, 8/14 edition

A circuit motif in the zebrafish hindbrain for a two alternative behavioral choice to turn left or right, Minoru Koyama, Francesca Minale, Jennifer Shum, Nozomi Nishimura, Chris B Schaffer, Joseph R Fetcho

Coordination of Brain Wide Activity Dynamics by Dopaminergic Neurons, Heather K Decot, Vijay MK Namboodiri, Wei Gao, Jenna A McHenry, Joshua H Jennings, Sung-Ho Lee, Pranish A Kantak, Yu-ChiehJill Kao, Manasmita Das, Ilana B Witten, Karl Deisseroth, Yen-YuIan Shih, and Garret D Stuber

Convergence of visual and whisker responses in the primary somatosensory thalamus (ventral posterior medial region) of the mouse, Annette E Allen, Christopher A Procyk, Timothy M Brown, Robert J Lucas

Generating Natural Language Descriptions for Semantic Representations
of Human Brain Activity, Eri Matsuo, Ichiro Kobayashi, Shinji Nishimoto, Satoshi Nishida, Hideki Asoh

Complementary mechanisms create direction selectivity in the fly, Juergen Haag, Alexander Arenz, Etienne Serbe, Fabrizio Gabbiani, Alexander Borst

Statistical mechanics of ecological systems: Neutral theory and beyond, Sandro Azaele, Samir Suweis, Jacopo Grilli, Igor Volkov, Jayanth R. Banavar, and Amos Maritan

Human inferences about sequences: A minimal transition probability model, Florent Meyniel, Maxime Maheu, Stanislas Dehaene

Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells, Loïs S Miraucourt, Jennifer Tsui, Delphine Gobert, Jean-François Desjardins, Anne Schohl, Mari Sild, Perry Spratt, Annie Castonguay, Yves De Koninck, Nicholas Marsh-Armstrong, Paul W Wiseman, Edward S Ruthazer

Human collective intelligence as distributed Bayesian inference, Peter M. Krafft, Julia Zheng, Wei Pan, Nicolás Della Penna, Yaniv Altshuler, Erez Shmueli, Joshua B. Tenenbaum, Alex Pentland

Temporal Horizons and Decision-Making: A Big Data Approach, Robert Thorstad, Phillip Wolff

Unrelated to all that, 8/13 edition

UKIP (and brexit?) is driven by perception of immigration, not actual immigration.

What is the best classifier in machine learning? One paper suggested that we should all just go to random forests straight away. But then, maybe not. So… do whatever you were doing before? Anyway, thanks to this I learned about XGBoost.

When you eat a dried fig, you’re probably chewing fig-wasp mummies, too. Learn everything you can about figs and wasps and fig wasps!

Do animals fight wars and if so what was the largest war? This is the story of Argentine ant and its continent-spanning supercolonies.

The NIH postdoc salaries are out for the year and you can see the Obama pay raise! …if you are a 0- or 1-year postdoc, that is.

Here is the Standard Model of physics in one equation (click through for an explanation):

sml

Are markets efficient? A good discussion between Fama and Thaler. Unsurprisingly, a lot of it comes down to semantics.

Did the human brain evolve to speak multiple languages? I think the historical evidence is a resounding yes.

A ‘brief’ history of neural networks. I liked this from part four:

So, why indeed, did purely supervised learning with backpropagation not work well in the past? Geoffrey Hinton summarized the findings up to today in these four points:

Our labeled datasets were thousands of times too small.
Our computers were millions of times too slow.
We initialized the weights in a stupid way.
We used the wrong type of non-linearity.

More on the legacy of HM; or, journalists behaving badly

Well that was fast. The book excerpt on HM and Corkin has gone over like a lead balloon. Here are some excerpts of a statement by Jim DiCarlo, head of BCS at MIT:

1. Allegation that research records were or would be destroyed or shredded.

We believe that no records were destroyed and, to the contrary, that Professor Corkin worked in her final days to organize and preserve all records. Even as her health failed (she had advanced cancer and was receiving chemotherapy), she instructed her assistant to continue to organize, label, and maintain all records related to Henry Molaison. The records currently remain within our department.

2. Allegation that the finding of an additional lesion in left orbitofrontal cortex was suppressed.

The public record is clear that Professor Corkin communicated this discovery of an additional lesion in Mr. Molaison to both scientific and public audiences. This factual evidence is contradictory to any allegation of the suppression of a finding.

3. Allegation that there was something inappropriate in the selection of Tom Mooney as Mr. Molaison’s guardian.

Mr. Dittrich identifies some individuals who were genetically closer to Mr. Molaison than Mrs. Herrick or her son, but it is our understanding that this family took in Mr. Molaison and his mother, and took care of Mr. Molaison for many years. Mr. Mooney was appointed conservator by the local court after a valid legal process, which included providing notice of a hearing and appointment of counsel to Mr. Molaison.

So: no research records destroyed, no attempt to suppress the lesion, nothing inappropriate about asking a very-extended family member that had already been taking care of HM for many years to be his conservator.

It will be interesting to see the re-rebuttal. Assuming that the author recorded the conversation, he would have a direct quote from Corkin saying she would shred the documents. And assuming that the author has the e-mails and paper revisions, you would Corkin attempting to delete the lesion data from the initial versions of the paper – unless the author has totally taken that out of context.

I would love to hear from the fact-checkers at the publishing house…

Update – from the comments below, Neuroskeptic points to the re-rebuttal from the author of the original piece. Basically sums up my ‘interesting’ statement above which is: they have sources and evidence for all of the assertions (such as recordings, etc).

The legacy of HM; or, scientists behaving badly

There is a book about Henry Molaison (HM) that will be coming out tomorrow and it is already causing a bit of a fuss in the scientific community. There is an excerpt in the New York Times Magazine which investigates how the lead researcher (Corkin) dealt with her authority, especially after HM passed away. It kind of has to be read to be believed:

…Despite what she said during the meeting, Corkin’s central problem with the paper, the one she pushed back on hardest, wasn’t Annese’s chatty writing style. Instead she was concerned with something Annese had discovered in Henry’s brain.

Specifically, Annese’s analysis had revealed a previously unreported lesion in Henry’s frontal lobe. The lesion was in the left hemisphere and appeared to have been caused by a man-made object…As one of the paper’s anonymous peer reviewers pointed out, “much of the neuropsychological literature on H.M. has made the case that so-­called frontal function was intact.”

When Corkin sent Annese her revisions of his paper, she deleted all references to the newly discovered frontal lesion. In a note to Annese, she explained that “the frontal lobe lesion does not appear on either the in situ scans [the M.R.I. scans made while the brain was still in Henry’s skull] or the fresh brain photos” and that “any consideration of it would be highly misleading.” Annese responded with a series of images from in situ M.R.I. scans that, contrary to Corkin’s assertions, gave clear views of the lesion.

The paper has since been published here. Here is the (fairly clear) lesion which can also be seen in old (1991-92) MRIs:

HM frontal lobes

Then it turns out that the ‘next of kin’ that became his conservator, donating HMs brain and consenting to further experiments, was not only chosen by Corkin but also was not remotely his next of kin.

Eventually, over the phone, Mooney told me that he and Henry were third cousins, very distant relations.

I asked Corkin whether she was aware that when Mooney became Henry’s conservator, one of Henry’s first cousins, Frank Molaison, was living nearby — his actual next of kin — and had not been consulted. I mentioned that his name should have made him particularly easy to find.

“I was not aware of his existence,” she said.

I asked whether she had ever done any genealogical research at all into the man she had studied for almost a half-­century.

“No,” she said.

I had tracked down and spoken with Henry’s closest living relatives, and some were surprised and disturbed to learn about the things Corkin and her colleagues did with their cousin while he was alive and about the fight over his brain that took place after his death.

I asked Corkin why she arranged for Mooney to apply to become Henry’s conservator in the first place. I knew that for more than a decade before Mooney was named Henry’s conservator, Henry himself had been the only one signing the consent forms for his experiments.

“I just wanted another level of security,” Corkin said. “Another person who was not amnesiac and who had Henry’s best interests at heart.”

I asked what she meant by “security.” Security from what?

“For Henry,” she said. “For M.I.T.”

And what were M.I.T.’s vulnerabilities?

“I don’t know,” she said. “I’d have to ask our lawyers that.”

Someone posted HM’s informed consent form, which claims that HM’s close relatives had passed away which is…clearly not true if his cousin by the same surname lived nearby.

And hey, the whole thing only gets worse (emphasis added):

Me: Right. And what’s going to happen to the files themselves?

(She paused for several seconds.)

Corkin: Shredded.

Me: Shredded? Why would they be shredded?

Corkin: Nobody’s gonna look at them.

Me: Really? I can’t imagine shredding the files of the most important research subject in history. Why would you do that?

Corkin: Well, you can’t just take one test on one day and draw conclusions about it. That’s a very dangerous thing to do.

Me: Yeah, but your files would be comprehensive. They would span decades.

Corkin: Yeah, well, the tests are gone. The test data. The data sheets are gone. Because the stuff is published. Most of it is published. Or a lot of it is published.

Me: But not all of it.

Corkin: Well, the things that aren’t published are, you know, experiments that just didn’t … [another long pause] go right. Didn’t. You know, there was a problem. He had a seizure or something like that.

And on and on. Read the article in full, it is pretty mindblowing (and full of great gossip). Neuroskeptic wrote a review of the full book earlier in the summer which has some other interesting morsels.

As written, a charitable reading of the article is that Corkin did not want to try too hard to wrestle with the ethics of her experiments on this man’s life, wanted to willfully ignore any complicating evidence, and saw no need for others to look at her data. Charitably.

Update

Some push back on the article from a couple of groups. First is Earl Miller and 200 neuroscientists (who?) with the following letter to the NYT:

“We are a community of scientists who are disturbed by a recent New York Times Magazine article (“The Brain That Couldn’t Remember”), which describes Professor Suzanne Corkin’s research in what we believe are biased and misleading ways. A number of complex issues that occur in research with humans, from differing interpretations of data among collaborators to the proper disposition of confidential data, are presented in a way so as to call into question Professor Suzanne Corkin’s integrity. These assertions are contrary to everything we have known about her as a scientist, colleague, and friend. Professor Corkin dedicated her life to using the methods of neuropsychology to illuminate how the brain gives rise to the mind, especially how different regions of the human brain support different aspects of memory. Her scientific contributions went far beyond her work with the amnesic patient HM (whose well being she protected for decades), with major contributions to understanding clinical disorders such as Alzheimer’s and Parkinson’s disease. She was a highly accomplished scientist, an inspiring teacher, a beloved mentor to students and faculty, and a champion of women in science. While her recent passing is a great loss to our field, her passion and commitment continue to inspire all of us. We only regret that she is not able to respond herself.”

Second is Jenni Ogden who reviews the book in Psychology Today. It puts the above in more context but I don’t see it really rebutting any of the key points.

I am hearing on twitter that Corkin did not, in fact, shred documents but do not understand how that jives with the above direct quotation. “A full rebuttal” is on its way.

Papers for the week, 8/7 edition

Vision Guides Selection of Freeze or Flight Defense Strategies in Mice,
Gioia De Franceschi, Tipok Vivattanasarn, Aman B. Saleem, Samuel G. Solomon.

How Structured Is the Entangled Bank? The Surprisingly Simple Organization of Multiplex Ecological Networks Leads to Increased Persistence and Resilience,
Sonia Kéfi, Vincent Miele, Evie A. Wieters, Sergio A. Navarrete, Eric L. Berlow.

Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust, Dongjin Seo, Ryan M. Neely, Konlin Shen, Utkarsh Singhal, Elad Alon, Jan M. Rabaey, Jose M. Carmena, Michel M. Maharbiz.

Thirst neurons anticipate the homeostatic consequences of eating and drinking, Christopher A. Zimmerman, Yen-Chu Lin, David E. Leib, Ling Guo, Erica L. Huey, Gwendolyn E. Daly, Yiming Chen & Zachary A. Knight.

Operation of a homeostatic sleep switch, Diogo Pimentel, Jeffrey M. Donlea, Clifford B. Talbot, Seoho M. Song, Alexander J. F. Thurston & Gero Miesenböck.

The Basis of Food Texture Sensation in Drosophila, Yali V. Zhang, Timothy J. Aikin, Zhengzheng Li, Craig Montell.

On the Encoding of Panoramic Visual Scenes in Navigating Wood Ants, Cornelia Buehlmann, Joseph L. Woodgate, Thomas S.

A rodent model of social rejection,  Haozhe Shan, Inbal Ben-Ami Bartal, Peggy Mason.

Posterior parietal cortex guides visual decisions in rats, Angela M. Licata, Matthew T. Kaufman, David Raposo, Michael B. Ryan, John P. Sheppard, Anne K. Churchland.

The common neural parasite Pseudoloma neurophilia causes altered shoaling behaviour in adult laboratory zebrafish (Danio rerio) and its implications for neurobehavioural research, S Spagnoli, J Sanders, M L Kent.

A Probability Distribution over Latent Causes, in the Orbitofrontal Cortex, Stephanie C. Y. Chan, Yael Niv, and Kenneth A. Norman.

Neurons in Macaque Area V4 Are Tuned for Complex Spatio-Temporal Patterns, Anirvan S. Nandy, Jude F. Mitchell, Monika P. Jadi, John H. Reynolds.

Unrelated to all that, 8/6 edition

Ten simple rules for writing a postdoctoral fellowship and Ten simple rules for curating and facilitating small workshops

The super-recognizers of Scotland Yard:

In 2007, Neville had set up a unit to collate and circulate images of unidentified criminals captured on CCTV. Officers were asked to check the Met’s “Caught on Camera” notices to see if they knew any of the suspects. “It became apparent that some officers were much better than others,” Neville told me. “For example, if I received 100 names, some officers would have submitted ten or 15, while in the main they were one-off identifications.”…Met officers trawled through tens of thousands of hours of CCTV footage, ­identifying 609 suspects responsible for looting, arson and other criminal acts. One officer, PC Gary Collins, made 180 identifications, including that of one of the most high-profile suspects…

See also this paper on super-recognizers

National Geographic Travel Photographer of the Year 2016

Even though there were a lot of people in Ben Youssef, still here was more quiet and relaxing compare to the street outside in Marrakesh. I was waiting for the perfect timing to photograph for long time.

Even though there were a lot of people in Ben Youssef, still here was more quiet and relaxing compare to the street outside in Marrakesh. I was waiting for the perfect timing to photograph for long time.

I found this open on my mobile browser window one day and I don’t remember why, but am thankful to Past Me:

CpBc8srWEAAQZqQ

“I have a great idea! Let’s get neural networks to build faces!”

ANN faces

OTOH they can infer 3D images of cars pretty well (this is a Big Deal)

What are some of the best algorithms of the 20th century?

We’ve been understanding the Faraday cage all wrong:

So I started looking in books and talking to people and sending emails. In the books, nothing! Well, a few of them mention the Faraday cage, but rarely with equations. And from experts in mathematics, physics, and electrical engineering, I got oddly assorted explanations. They said the skin depth effect was crucial, or this was an application of the theory of waveguides, or the key point was Babinet’s principle, or it was Floquet theory, or “the losses in the wires will drive everything…” And then at lunch one day, colleague n+1n+1 told me, it’s in the Feynman Lectures [2]! And sure enough, Feynman gives an argument that appears to confirm the exponential intuition exactly. [The problem is, it is wrong.]

Everything you wanted to know about hair

Every number tells a story