Failed interview with Human Brain Project director Katrin Amunts

Human Brain Project is supposed to be half-way onto simulating the human brain in a supercomputer, the €1 Billion EU project withstood all criticisms, protests, ridicule and mutinies, from inside and outside, and even escaped proper evaluation. Its last remaining challenge on the road to full success is the overbearing masculinity in its leadership ranks, which HBP was apparently asked by the EU to act upon after my tweets during a HBP conference. Maybe this was why HBP Executive Director Chris Ebell resigned just this month?

In that regard I was keen to interview the only woman among HBP leaders, the scientific director Katrin Amunts, professor for Brain Research at the University of Düsseldorf and director of the Institute of Neuroscience and Medicine in Forschungszentrum Jülich (FTJ). In November 2017, I published an interview with Thomas Lippert, one of the HBP leaders and director of the Institute for Advanced Simulation at FZJ. I then invited Amunts, who on 20 November 2017 agreed to do an interview by email. I sent my questions the next week, which Amunts described as “interesting, but not easy to answer”.  In January I sent New Year wishes with a discreet reminder, to which Amunts replied that she is currently preparing the answers to my interview questions. In March 2018, Amunts replied again that she is “on it, to answer all questions and the manuscript already has a veritable size of several pages”. Amunts never contacted me since. My last reminder was on 29 April 2018, it went unanswered.

This is therefore a non-interview with HBP scientific director Katrin Amunts, who changed her mind and never answered my questions.

 

 

 

 

 

 

 

After such a long wait, I decided to publish instead of Amunts’ unavailable replies some random bits I picked off the HBP website. I invite my readers to provide their own stand-in replies in the comment section. Or maybe Prof Amunts will return to the interview eventually.

Katrin Amunts was born in the communist Eastern Germany (GDR), she learned Russian and went to study medicine in 1981 at the Pirogov Institute in Moscow, in USSR. Afterwards, she stayed for a PhD at the Federal Centre for Mental Health of the Academy of Sciences of USSR, her thesis was titled “Quantitative analysis of the cytoarchitecture of area 4 of human brain cortex in ontogenesis“. The associated Moscow Institute of Psychiatry featured a huge collection of human brain samples, due to the special legal situation in Soviet Union, which basically allowed the state to do whatever it wanted with its citizens, especially deceased ones. A unique research situation, even if retrospectively ethically wanting.

Some of Amunts’ publications on brain architecture from those times can be traced to a GDR colleague working at the Moscow Institute of Psychiatry, Karl-Heinz Pollak (Amunts is listed under her former name Fiedler here). She defended her thesis just as the socialism in Eastern Europe was collapsing and her own country ceased to exist, the Soviet Union soon followed suit. In 1993, after a brief stay in Berlin, Amunts moved to the West, to work with the neuroscience professor Karl Zilles, head of C. & O. Vogt Institute at the University of Düsseldorf . In 2013, she was appointed as Zilles’ successor there.

Together with Zilles, Amunts developed highly advanced software tools and detailed maps of human brain architecture. She was able to neatly transfer her skills in analysing human brain sections from Moscow to Zilles’ institute in Düsseldorf. Their two seminal papers were:

Amunts K1, Istomin V, Schleicher A, Zilles K. Postnatal development of the human primary motor cortex: a quantitative cytoarchitectonic analysis. Anat Embryol (Berl). 1995 Dec;192(6):557-71.

and

Amunts K1, Schleicher A, Zilles K. Persistence of layer IV in the primary motor cortex (area 4) of children with cerebral palsy. J Hirnforsch. 1997;38(2):247-60.

These cytoarchitectural studies of human motor cortex were made possible thanks to the unique collection of human donor brains of all ages. Because the two papers indicate no origins, one must assume those brains belonged to C. & O. Vogt Institute and were acquired according to German ethical standards in Düsseldorf surroundings or other clinics of Western Germany. This impressive Düsseldorf collection of  human brain sections from “54 individuals ranging in age from birth to 90 years” as well as “14 children (age: 3-13 years) with cerebral palsy” plus 33 “control” child brains, was at least as extensive as the Soviet one which Amunts left behind at the Moscow Institute of Psychiatry.

Amunts and Zilles became experts of brain cortex structure and its digital analysis worldwide. Their technology, “a new approach to cortical mapping”, modified from the previously developed method at Zilles lab (Schleicher et al 1986, Schleicher & Zilles 1990), was released as advanced version to public in 2005 (Schleicher et al, 2005) and then again in 2009, in updated form, yet under the same title and in a different journal, as Schleicher et al 2009.

All in all, Amunts is THE expert in brain architecture, brain pathologies and digital neuroscience technologies. It is a pity therefore she negated on her promise to help my readers understand how brain and brain diseases are to be simulated in Human Brain Project. So here are my questions, with bits off the HBP website arbitrarily used as a stand-in.

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1. Your own research platform is about human brain structure. In this video, you explain the approach: thin-sectioning of donated human brains, in order to scan those and assemble a 3D computer model.

 

 

 

 

 

Yet this says nothing about the actual neuronal structure and connectivity of the brain on the cellular and intracellular basis. How do you intend to map all the neurons at HBP? Your site says: “3D-PLI allows to map nerve fibers and fiber tracts in whole postmortem brains with a resolution of a few micrometers“. In this interview, you say it is 20 micrometers (and that you are confident the brain can be decoded by HBP). That is not really close enough to properly distinguish individual neural fibres, never mind synapses. How would you comment on these limitations? How will you fill the huge predictable gaps from the scanning data?

“A simpler approach has thus been adopted to produce results that are increasingly close approximations to experimental data. Simulation takes place at several separate organisational levels in the brain, ranging from the molecular though the subcellular to cellular and up to the whole organ. The level of detail decreases as the level rises towards the whole organ.

At the microscopic level and below, the signalling between neurons is the focus. Neurons are electrically excitable cells that transmit messages to each other across the synapses. These messages are crucial to the normal functioning of the central nervous system.
The macroscopic level examines assemblies of neurons, and their roles within the brain”.

2. Your own website says: “This model will not only help reveal the neurobiological basics of mental capacities, but will also enable characterization of their individual facets and underlying mechanisms.” Could you explain how a map of a brain, if it was ever achieved with the tools available, can give insights into how the brain actually works?

“To create a map of the human brain’s structure, post-mortem brains are cut into 6,000 to 7,000 extremely thin slices (each slice is 20 micrometres thick—it takes about five to six month’s work to slice an entire brain). The slices are scanned and then digitally reassembled to explore the structure and connections of the brain down to the level of individual nerve fibres”.

3. The HBP approach is to map all the neurons of the brain of a human and a mouse. But what about glia cells, the astroglia and oligodendroglia? Those are active and necessary cells of a brain (astroglia are even electrophysiologically active), without which the brain will not be able to function at all, or, on the smaller scale, to process the signals correctly. Which department at HBP addresses the glial networks, and how is this work being integrated?

“However, the challenge is a complex one, as the human brain contains 86 billion brain cells (known as neurons) each with an average 1,750 connections to other neurons (known as synapses). Current computer power is insufficient to model a entire human brain at this level of interconnectedness.”

4. You suggested in a presentation here the brain would never need or use replacement parts.

 

 

I understand this was a simplification for didactic purposes, since neural and glial cells are generated from the pool of neural stem cells throughout lifetime, even in old age. How does HBP intend to incorporate the neurogenesis aspect in the mapping process? Which HBP partners are involved in this?

“In 2016, we published passive models of human L2/3 pyramidal cells. These models showed that the specific membrane capacitance (C_m) of these neurons is ~0.5 µF/cm², half of the commonly accepted ‘universal’ value (~1 µF/cm²) for biological membranes.

We have now extended the passive models of human L2/3 to estimate also the synaptic properties, in particular the NMDAR-kinetics, and to estimate the properties of the ion channels underlying the somatic/axonal spiking mechanisms.
In the near future, we plan to expand our research to other neurons in the human cortex, including inhibitory neurons, and to build a model for each of them. Connecting these neuronal models via synaptic models will allow us to simulate activity of a human cortical column.”

5. After some initial uncertainty, it does look like one of the main goals of Human Brain Project is to simulate the human brain in a supercomputer. You yourself said in an interview in 2017: “By then, we should have computers that enable us to keep an entire human brain model in the memory on a cellular level and analyse it. In 20 years, I should think we’ll have realistic simulations of a human brain at nerve cell level that factor in the most important boundary conditions“. Your FZ Jülich colleague and HBP partner Prof Thomas Lippert did say in an interview with me that brain simulation should be just as doable as simulating weather or climate. How would this simulation happen, which biological input will the supercomputer need? Can HBP achieve the goal of collecting all this input?

“Can you imagine a brain and its workings being replicated on a computer? That is what the Brain Simulation Platform (BSP) aims to do. The BSP is available to researchers worldwide, so that they can compare their experimental results with model predictions and conduct investigations that are not possible experimentally”

[..]

One of the major tasks of the HBP is to simulate the rodent brain; but what can be learnt from that on the human brain? Here, we characterise the biophysical and computational properties of human neurons. Are human neurons similar to rodent neurons? What are the differences? How may we integrate these into the simulations? And may these differences explain the cognitive capabilities of humans?”

6. In this interview, you also mentioned that HBP works on understanding what consciousness is. Which tools are being applied for this? How can the brain atlas contribute?
Also, where do you see consciousness first appear in the evolution? Is it a unique human feature, or an intrinsic function of every complex biological neural system, even if it is not even a central brain as such (see cephalopods)? If the latter, how can any brain be ever simulated in our supercomputers?

“Imagine an apple — its greenness, sour taste and its fresh, crisp crunch; how does the brain create a representation of such an apple?

This is one of the questions the Human Brain Project (HBP) is asking. To better understand the human brain, you need theories, models and conceptual frameworks, which can be tested and refined. The HBP is supporting the work of cognitive and theoretical neuroscientists to unlock deeper insights into the workings of our brains.

Theoretical neuroscientists are working to develop a multi-scale theory of the brain that synthesises top-down and data-driven bottom-up approaches. They are also trying to: unify theories of learning, memory, attention and goal-oriented behaviour; understand complex cognitive functions such as spatial navigation, recursion, and symbolic processing; and identify bridges linking the multiple temporal and spatial scales implicated in brain activity and in the signals captured by imaging and other technologies”.

7. In this regard, I presume also HBP is aware that the brain does not compute the way our (super-)computers compute. Otherwise there would not be a huge focus on developing neuromorphic computing in HBP. I am puzzled hence how HBP plans at the same time to simulate neuronal functions of an entire mammalian brain in a normal computer, and try to emulate the most basic neuromorphic information processing function by developing new technology quasi from scratch. It does look a bit like putting a cart ahead of a horse, but how do you see this?

“Neuromorphic computing implements aspects of biological neural networks as analogue or digital copies on electronic circuits. The goal of this approach is twofold: Offering a tool for neuroscience to understand the dynamic processes of learning and development in the brain and applying brain inspiration to generic cognitive computing. Key advantages of neuromorphic computing compared to traditional approaches are energy efficiency, execution speed, robustness against local failures and the ability to learn.”

8. HBP’s goal is still also to simulate brain diseases in order to find potential cures. E.g.:

 

Which diseases for example, and how would this happen? Could you give some neuroscience insights in the approach?

“If a single brain scan can tell us a huge about one patient with one condition, how much more could we learn if we could compare every scan of every patient with that condition?

The HBP’s Medical Informatics Platform (MIP) seeks to advance brain medicine, by using computer science to allow researchers around the world to exploit medical data, regardless of where it may be stored and to create machine-learning tools that can search this data for new insights into brain-related diseases.”

9. HBP apparently considers mouse brain as a simple enough model to fall back on if human brain simulation cannot be achieved. Yet neuroscientist Prof Wim Crusio commented in this regard:
“If I would have to evaluate as reviewer a research proposal aiming to simulate a Drosophila brain on a €1bn budget over 10 years, I’d nix them for being overly optimistic. If the aim were to simulate a mouse brain, I’d inquire as to what they had been smoking when they wrote that application and recommend they start taking their meds again. Simulating a human brain? Comparing that with simulating materials and such? I’m afraid I’d actually be left speechless, although probably rolling on the floor howling with laughter…”
How would you, as neuroscientist peer, go and dispel Prof Crusio’s concerns?

“Simulation also aims to replicate work on animal models, such as the mouse. In addition, the computing environment used for simulation offers the possibility of studying disease processes electronically. […]

In the context HBP Neurorobotics research (SP10) the whole brain model is connected to a virtual mouse body that is embedded in a dynamic environment. In the context of HBP’s cross disciplinary research (CDP1) this embodied brain model is used to model in vivo experiments on motor rehabilitation after stroke. Ultimately, we aim at simulating behavioural experiments such as whisking and grasping. Future refinement of the whole-brain model therefore focuses on brain regions that are involved in sensory-motor processing”.

10. Another neuroscientist, Dr Mark Humphries, is wondering what the scientific rationale of Blue Brain is. His concerns precisely are that the Blue Brain uses two-week old rats as source of data, also that non-primate prefrontal cortices lack the so-called “granular layer IV“. What exactly does Blue Brain bring to the HBP to understand an adult human brain? Can you comment as both neuroscientist and HBP scientific director?

“Non-HBP researchers and groups worldwide are invited to apply for using HBP Platform features. The aim is to open the HBP Platform infrastructure to meet the needs of the user community in a new dynamic way.

The Call is open to all non-HBP researchers, with target groups from academic, non-academic and medical research (including hospitals), and industry and pharma (SMEs and companies).

The voucher programme aims to establish successful win-win collaborations and pursue technology innovation and engineering solutions of mutual interest and benefit. The idea is that interested applicants get in contact with the HBP during the application process to work together on the proposals. For more details and contacts, please read the “Guide for Applicants” and see the “Proposal Template” under “Files” at the bottom of the call site.”

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Update 4.09.2018: just some hours after that post was published, on August 30th, Katrin Amunts wrote to me offering to answer my interview questions. She said the replies will be finalised very soon. I am now waiting replace the place holders, this article might be then split in a two-part-installment!

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