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On the wiring of female and male brains

The data in the study concerned are derived from a technique called 
diffusion tensor imaging (DTI), which estimates how water diffuses along 
white matter tracts in the brain. The big advantage of DTI is that it 
can be used in living humans. Its big disadvantage is that even at best 
it gives only a very low resolution and thus partial picture of possible 
connections in the brain, and DTI is also rather poorly validated 
against 'gold standard' anatomical tracing methods that are routinely 
used in animal experiments. Thus, of the billions of connections made 
via the white matter of the human brain, DTI detects a tiny fraction of 
a percent and the method only indicates hypothetical anatomical 
connections and not any function. As a reality check one should take the 
example of the nematode worm, C elegans, which is the only animal for 
which we have a complete map of every connection in its nervous system. 
It has 302 neurons, compared to 85 billion in the human brain, yet no 
neuroscientist (or journalist) can tell you what is in the mind of this 
worm. Our knowledge of the connections in the human brain is 
poverty-stricken by comparison, yet this has not stopped some 
neuroscientists from linking their hypothetical structures of human 
neural networks, derived from techniques like DTI, directly to complex 
psychological process, as in the paper under discussion. Worse still, 
the media reinterpret and amplify the scientists conjectures to build 
their own confection of irresponsible speculation that bears little 
relation to the original data, as the present case so ably illustrates. 
- K. Martin 

Please believe my results!

»I don’t believe a word of what you say.«
My supervisor shook his head. »This effect is minimal. How do you want to argue it is relevant at all?«
I stared at him in surprise. Couldn’t he see that my data were significant, even if only marginally? Should all my efforts count for nothing? Was he seriously suggesting that there was a flaw in my reasoning? Did I need to reconsider my basic assumptions? Could it really be that my scientific investigations led to a deceptive conclusion?
So I went and pondered over my research. Research – what was I searching for? Knowledge? Wisdom? Truth? Solutions to overcome our human weaknesses and limitations? Fame? Recognition? Self-affirmation? Power? Progress?
Obviously my current results could not satisfy my thirst for knowledge. In the end, it didn’t matter if there were more excitatory than inhibitory neurons, which were the names of the many proteins involved in the presynaptic machinery and what fraction of brain connections could be called long-range rather than local.
Or could these findings point to more important answers? Could they help us understand who we are, why we can rightly assume that we are able to think logically, why we strive to make sense of our lives and the universe we find ourselves in?
After all, science influences our perception. The more we learn about the incredible dimensions of space, the more we fall silent in awe. The Earth – an isle teeming with life – seems so infinitely insignificant. On the other hand, we find similar orders of magnitude when we replace the telescope with the microscope. So physical size may be the wrong indicator of relevance. Studying biological systems at different scales has been a inexhaustible source of inspiration for technical achievements – or should we call them imitations?
Smiling again, I leaned back. Surely my investigations promised to remain interesting; they might even reveal new secrets. At least they would have an impact on me.
And hopefully my next findings would be convincing, so that others didn’t have to believe in my results, but would only believe in the (well-founded) conclusions they drew from them.

- F. S├Ągesser

Capo Caccia 2013

See also the Capo Caccia report on the INI webpages!

It has been almost a month since we came back from Sardinia, Italy, where the
CapoCaccia Cognitive Neuromorphic Engineering Workshop took place. I felt somewhere in between nostalgic and sad that it was over, and it took me some days to get used to the old routine without the sea, the sun and the approximately 130 amazing workshop participants.
How it all started

The conference runs every year since 2007, but this year was the first time that I had the opportunity to attend. 
With a biomedical background I must confess the name of the conference was equally imposing, as it is for you -reader without any background- in “Neuromorphic Engineering”-. FYI neuromorphic engineering aims at developing new computing principles and technologies based on neurobiological architectures. Examples are silicon retinas, cochleas and neurons that mimic the ones that you have in your nervous system.
I started hearing about this workshop when I was an MSc student and it was hard to picture the conference and the place. Just from listening to what people said I felt like there was a clear analogy between the TV series LOST and Capo Caccia. The title of the TV series perfectly described my initial feelings! Moreover, both TV show and meeting take place in a hidden island where scientists are working on “mysterious” topics not unlike the Dharma Initiative in the show. I had also heard that both are isolated and far from civilization. My first suspicions were confirmed, as indeed the hotel was nowhere near the city center.
The conference started and I seriously did not know what to expect but it was definitely not conventional from the beginning. What first caught my attention was the setup of the conference room; the chairs were all close to one another in a half moon shape bringing everyone in close proximity. After the introduction the first speaker started drawing on a flip-chart, yes… on paper, no power point presentations, they were completely prohibited. As the presenters need to draw, they have to go step by step with their explanations right from the beginning and even if you are not working on the same field you can more easily follow. The dynamics of the presentation allowed breaking the wall between the presenter and the rest of the participants where discussions and questions were a constant. It was definitely not a one-man show. If you have attended any other, more conventional scientific meetings you know exactly what I am talking about.

Also the workshop offered a smooth transition within the two weeks from biology to neuromorphic engineering going through different topics and different high- quality presenters with different points of view. This is the only way to follow a story from different angles. Some of the topics discussed were cortex, learning, winner-take-all networks, neuromorphic devices, chips, robots, SpiNNaker, NEF, etc.
Another non-conventional aspect of the meeting is that although it has a time structure, there is flexibility in the sense of the topics to be addressed. Depending on the clear interests that are being shown during the first days, the subjects, discussions and meetings change.
The conference had also a cool disco not really for dancing, well occasionally… but for setting up all the different robots and computers. Most of the demos took place here:

Not everything is about learning from someone else’s presentation but instead we could choose from a list of projects where mostly PhD students were leading the group. You could choose any group you liked and the point was to keep you busy during the afternoons with the purpose of learning something new in a similar or completely different topic as your own. You can read more about the projects here:
Definitely for me the coolest was that you could have breakfast with a neuroscientist, coffee with an engineer and dinner with a theoretician and multiple combinations of the above along the day. In a scientific environment this could not be better. This is actually possible because all participants were staying at the same place, the hotel is not huge and the fact that it is not so simple to escape get out of the hotel account for a very natural interaction that would otherwise be impossible in other conditions.

 Why would you like to go there?

Science and technology advance at huge steps nowadays and it is not longer possible to make progress by just considering our own field. The only way to advance is by combining different subjects. So if you are a biological neuroscientist you can go there to learn what people are doing in engineering with the information you and people in your field have been providing and if you are an engineering you should go to see in which topics you can apply your technologies.

In conclusion Capo Caccia is a two-week workshop where theoretical and experimental neuroscientists (and physicists, engineers, mathematicians, psychologists, etc.) from around the world meet to discuss, learn and work on different topics related to neuromorphic engineering.
If you want to read more about the conference go to:

Here a couple of pictures so you can get an idea:

And yes, we had a very nice time.

- G. Michel

The Boy Who Cried Gold

Last 10th of April the prestigious journal Nature published a novel imaging technique that allows the visualization of intact brain tissue in 3D. By getting rid of the lipids and using a polymer to fix the rest, the structure -with all its proteins and nucleic acids intact- can be preserved, while the whole tissue becomes transparent.

The paper had considerable media impact, and the following day the invisible brain was taking the online front page of many of the most popular newspapers worldwide. The opening of the article at the abc science site stated: “The era of slicing and dicing for neuro-researchers is over with the arrival of a see-through brain”. Incredible!

I immediately sent an email with the news to the whole institute, and then I headed towards the INI kitchen…. Although my skeptic self was trying to push this idea away, I feared for a moment to find Rita, John and Simone moaning in agony while looking with nostalgia old EM pictures at the screens of the zamel computer. Fortunately, I did not encounter this scenario, but I saw Nuno, who was preparing his morning coffee with his usual calmness, something that surprised me a little.

-So Nuno, did you hear about the news??? - I asked anxiously.
-What news? - He replied, with his eyes reflecting puzzlement behind his rounded glasses.
-About this new method, CLARITY! –I exclaimed- is it such a breakthrough??? Is the tedious EM going to be replaced forever???
-Oh… that …– Now his eyes had a sparkle of understanding, the same one that grandfathers have when children ask them too many why’s in a row- No no, it is not going to replace EM. It is an important new technique of course, as it offers some advantages, but we will still need the old methods to properly assess connectivity.
-B-b-but the news… - I bubbled. The sparkle at his eyes got stronger, but this time I could also see on it a trace of resignation.
-I know… -he said, and he accompanied that gleam with a half smile.

That day I found myself carrying the sparkle all over the INI. I was all the time being stopped by other excited master students, who had read the news and wanted to know more about this new and promising technique. We decided then to continue the discussion at our student’s monthly Apero, and to invite Nuno to talk about the real implications of the method.

Because of the transcendence of the discussion almost all of us were present -although I suspect that Asim and Dennis cooking abilities had also something to do-. After an hour of objective analysis, these are the main points that we extracted:

-The technique allows for deep light penetration imaging, as the processed tissue is transparent.  This seems very promising because 3D reconstructions can be made without slicing. One limitation however, is in the optics. Lenses that have a high numerical aperture -which will give you the resolution to image boutons- and large working distance for deep imaging are needed. As the authors themselves state in the paper: special adaptive optics for CLARITY need to be developed.

-The biggest limitation however comes from light microscopy itself. You cannot have as much resolution as EM, because a physical limit imposed by the light wavelength exists. EM would still be needed to image at the synapse level. The authors, aware of such limitation, manage to combine CLARITY with EM. Yet another problem arises here, as the lack of lipids makes the characterization of the synapses difficult.

- One of the main advantages of the technique is that it allows for molecular phenotyping while preserving the tissue intact for imaging. Furthermore, as it is very permeable-because of the lack of lipids- the proteins are more accessible, making the process way more efficient. The stability of the rest of the elements in the polymer also allows phenotyping for several rounds.

- Assuming that the adaptive optics problem is solved, it will be very useful to track long-range projections. The brain doesn’t need to be sliced, something that will make the reconstruction faster. However, if you additionally want to have information at the synaptic resolution, you need to use EM on smaller volumes.

From the points above, we see that this new technique presents some clear advantages. It may help us characterize brain circuits faster, but the key question here is, in Nuno’s words: how much faster is it going to make us?  CLARITY is great, but it is obviously not the goose that laid the golden eggs…

A couple of weeks after that event I received an email from my mum.  She was asking me about an article she had read at the newspaper that claimed: “Spanish researchers open a new path to prevent and mitigate epilepsy”.  As you may imagine, the sparkle came back to my eyes… In order to confirm my suspicion, I decided to check the original article. On it, the authors demonstrated that the transcription factor ATF5 is implicated in neural stress-induced apoptosis. By increasing ATF5 levels neuronal death was prevented, and as a model, they were using status epilepticus-induced neuronal death. I would define the correlation that the journalist made between this piece of research and its implications for epilepsy as “brilliant”. I proceeded then to write back to my mum, stating all the set of reasons that would turn the golden eggs goose into a humble fowl. More that an email it looked like a dissertation, so I don’t know if my mum actually ever read it...

The following week, however, she was sending me a pile of articles -you have to imagine me sighting now…- hoping, I guess, that I would approve at least one of them. I didn’t. This time they were related to Parkinson or maybe Alzheimer, apparently it doesn’t seem to make much of a difference. In all the cases, an excellent research gets conveniently filtered and embellished when fallen into the media circus. This is passively observed by the authors, who I assume find themselves “trapped” into the middle of the situation. Quite convenient I would say…

Nonetheless, you may ask, isn’t media impact something positive for research? Doesn’t it bring social awareness and gives importance to our work? Of course! And that should be promoted. The difference is in how we do it. And the key question in here is the following: Do we want to be more the herald or the storyteller?  Are we willing to sacrifice our personal glory in favor of the future of science? This is something we all- the present and the future scientists- should keep in mind if one day a journalist knocks at our door.  Otherwise we take the risk to become, inevitably, the boy in our own tale, and it will no matter how long we keep crying.

- S. Soldado Magraner