What are the Unsolved Problems of Neuroscience?

By Neuroskeptic | February 28, 2015 3:34 am

In an interesting short paper just published in Trends in Cognitive Science, Caltech neuroscientist Ralph Adolphs offers his thoughts on The Unsolved Problems of Neuroscience.


Here’s Adolphs’ list of the top 23 questions (including 3 “meta” issues), which, he says, was inspired by Hilbert’s famous set of 23 mathematical problems:

Problems that are solved, or soon will be:
I. How do single neurons compute?
II. What is the connectome of a small nervous system, like that of Caenorhabitis elegans (300 neurons)?
III. How can we image a live brain of 100,000 neurons at cellular and millisecond resolution?
IV. How does sensory transduction work?

Problems that we should be able to solve in the next 50 years:
V. How do circuits of neurons compute?
VI. What is the complete connectome of the mouse brain (70,000,000 neurons)?
VII. How can we image a live mouse brain at cellular and millisecond resolution?
VIII. What causes psychiatric and neurological illness?
IX. How do learning and memory work?
X. Why do we sleep and dream?
XI. How do we make decisions?
XII. How does the brain represent abstract ideas?

Problems that we should be able to solve, but who knows when:
XIII. How does the mouse brain compute?
XIV. What is the complete connectome of the human brain (80,000,000,000 neurons)?
XV. How can we image a live human brain at cellular and millisecond resolution?
XVI. How could we cure psychiatric and neurological diseases?
XVII. How could we make everybody’s brain function best?

Problems we may never solve:
XVIII. How does the human brain compute?
XIX. How can cognition be so flexible and generative?
XX. How and why does conscious experience arise?

XXI. What counts as an explanation of how the brain works? (and which disciplines would be needed to provide it?)
XXII. How could we build a brain? (how do evolution and development do it?)
XXIII. What are the different ways of understanding the brain? (what is function, algorithm, implementation?)

While Adolphs’ suggestions are sensible and thought-provoking, I have doubts about some of them, especially the “complete connectome” questions. The set of connections within the brain is surely unique to each individual, and moreover, it changes over time (plasticity). So there will not be one complete mouse or human connectome. Instead, we ought to seek out the processes by which connections are formed and changed.

ResearchBlogging.orgAdolphs R (2015). The unsolved problems of neuroscience. Trends in cognitive sciences PMID: 25703689

CATEGORIZED UNDER: papers, science, select, Top Posts
  • Ibn al-Haytham

    I’m sensing some serious contradictions here:

    e.g. “IX. How do learning and memory work?”, “XI. How do we make decisions?” and “XII. How does the brain represent abstract ideas?” being solvable in a relatively very short time vs. “XVIII. How does the human brain compute?” being possibly insolvable.

    this is good one though: “XXI. What counts as an explanation of how the brain works?” my suggested answer is based on Feynman: “What I cannot create I do not understand” with the interpretation of “create” being “build a machine that does the same and I can map its required state variables to those of the system under study”

    of course, identifying the barriers that prevent me to do so at the moment is a very interesting thing in itself

    XXIII. What are the different ways of understanding the brain? (what is function, algorithm, implementation?) – this is not unsolved in the sense that we can give some sensible answers that may be superseded with better ones – but that’s the case with any scientific problem

  • Amber Worth

    XXIV Why the Roman numerals?

    • adc50

      Simple, this is terribly important stuff and Roman Numerals add incontestable gravitas and authority to the points being made . . .

      • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

        Agreed. Normal numerals are for plebs.

        • HoseyG

          Roman Numerals are clunky and outdated which is why they were replaced by the Hindu- Arabic numeric system. They are used purely as a device to show how clever you think you are by trying to be different. Trying using Babylonian numerals if you want to be the real deal.

    • Arayma

      Too hard for you?

  • Frank Kelly

    Given the advances in Genomics I think “XVI. How could we cure psychiatric and neurological diseases?” will be a lot closer than we think 5-15 years is my guess for at least some conditions.

  • Jespersen

    I wanted to read that article, but it was behind paywall. And now I don’t have to :)

    I’m a bit disappointed by how general some of the suggestions are, and how much of it is just linear extrapolation (caenorhabitis -> mouse -> human). If there’s anything we might have learned from the past, it’s that science rarely follows a straightforward path like this, and it doesn’t set a particularly reliable ‘program’ for solving problems.

    Then there’s the customary ‘explaining consciousness’ issue… which the author devotes just one point to, seems to ascribe entirely to neuroscience, and ignores specifics. Are we talking about neural correlates of consciousness? The binding problem? Or perhaps deeper understanding of consciousness by itself, in light of how many intuitive assumptions about it turned out to be wrong thus far (e.g. the difference between awareness & attention, or the fact that conscious experience is not a sequence of states, but a trajectory).

    Well, that’s my rant. But, like Ibn al-Haytham, I have to commend the author for the first meta-question, which is completely neglected way too often.

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  • Reginald Horky

    Actually, XVI and XVII have already been successfully completed with children. Whole consciousness initiation is a product of the dorsomedial striatium neurons elective access to the entire brain as compared to their use of primordial dorsolateral striatium neurons for lower MRI activities like reactions to fright with hide, flight, fight as well as reproduction and/or facility use. Briefly, Germany, Portugal, one of Europe’s elite college administration groups, the Coimbra Group has very successful programs for children and early adults and for their predictable recovery of the whole brain elect MRI activity of the medials and when children show signs of confined primordial lateral activity such as reading, linguistics, or logic difficulty. The applications of those whole consciousness recovery programs for adults probably are in use. El Salvador has instituted early-on educational programs that also maintain a child’s easily educated species born whole conscious capacities and with programs that are as simple as childhood preventative cult awareness. Cults are simply the result of “Emotionally Confined Educational Linguistics” of imposed as species unnatural in-brain confinements of thought initiation from the lowered MRI light activity of the lone/primordial dorsolateral striatium neurons, neurons that have very little to no capacity to make heads or tails of the purpose nor symbols of the Alphabet.

  • edgeoforever

    Depression – what are the causes? (saw 2 explanations so far – neurogenesis and inflammation) – and how to cure it

    • john gilmour

      Any head injury, or Extreme Emotional Trauma, can create a Brain Chemistry Imbalance causing Mood Disorders, and Depressions!
      the Normal evolutionary process, as we evolve from teen to adult, the body’s body, and brain Chemistry, and Hormones, go through a form of Metamorphosis, and keeping pace with the growth spurts, can cause Mood Disorders, and Depressions. become awkward and not uniform with the evolutionary process!

      The Cure, may be to rebalance our memory of the traumatic event
      such as imbedding the Forgiveness Process. As You cannot change the Past, however You Can Change, How you think of it!
      medication from a professional, is the first form of defence!

  • Wayne

    “The centerpiece of brain connectivity is the connectome–a comprehensive description of how neurons and brain regions are interconnected” Olaf Sporns, “Discovering the Human Connectome” for further reading.

  • TLongmire

    Your brain is a matrix that is dispensing substances known as neurotransmitters which don’t actually transmit anything but rather their purpose is to alter the rate and manner in which energy is affected. The resulting diffusion of energy is a 3-dimensional fractal continuously expanding outward in all directions or your ora which is being observed by a Consciousness at a given distance so it appears as a sphere. your ora could and perhaps is being observed at multiple distances giving rise to the sphere within spheres notion. As the observer perceives your ora it analyzes the resulting fractals (like divining the surface of the sun) and forms ideas within itself and then these ideas are conveyed back to you as thoughts to see how You react. This is either due to its choice or more likely due to the nature of “knowing” Let me deconstruct the word know for you, there is a line (l) intersected (->l) that diverges (->K) in (N) and around (O) to double you (W). The act of analyzing and conveying the information is perhaps the 1/2 to 2 second delay in “our” reality Didn’t Plato note that man by his nature is a member of a group which could be taken a step farther by saying man by his nature needs another to “be”. In this reality we are observed so that perhaps we become aware. So what I perceive as my conscious mind is my perception of the observed sphere (that hazy mirrored reflection) and my thoughts which are actually the interpretation of the observed sphere by another. My subconscious is the swirling chaos of the 3-d fractal while my higher consciousness is that part of the interaction that escaped the analysis of the observer and is expanding infinitely.

    • facefault

      There are several flaws in this claim.

      1) Neurotransmitters transmit information. They do this by binding to receptors and changing their conformation.

      2) “rate and manner in which energy is affected” is vague to the point of meaningless.

      3) Fractals can’t be 3-dimensional. Nor can they be 2-dimensional. Fractals have fractional dimension – their dimension isn’t an integer. (Yes, this is extremely weird. Here’s a pretty accessible explanation of how that can be: http://math.rice.edu/~lanius/fractals/dim.html ). For the same reason, a fractal can’t be a sphere, though it could be a close approximation to one.

      4) In what sense is the brain a matrix? It’s not a rectangular array. While cortical columns can be defined to some extent, the brain’s not nearly regular enough for a matrix to be as useful a description as other kinds of diagram.

      5) I think you mean “aura.” Also, auras aren’t really a thing.

      6) Presumption of telepathy.

      7) The half-second delay almost certainly comes from processing within the brain (http://www.tandfonline.com/doi/abs/10.1080/14681360500487470#.VPS9xrvLhBw ), not from interactions between the brain and outside environment. This part of your hypothesis is testable, though! Easiest way would be either isolating someone in the Pacific or Antarctica, or re-running an Apollo mission (https://what-if.xkcd.com/72/ ).

      • TLongmire

        The world at best is broken, but I’ll try to answer my faults.
        1. How could the changing shape of a molecule possibly generate consciousness?
        2. Place your hand in a creek it affects the water.
        3. A flame is nonmathmatical and yet exists, entropy may better convey essence.
        4. The brain is a matrix!
        5. I spelled it that way because it captures the essence O(denoting surrounding)RA(denoting emenating energy)
        6. Telepathy exists period! One doesn’t have to hear voices to know what another is thinking or feeling for that matter even from a distance.
        7. On several occasions I have perceived the delay and it always feels as though thoughts are being drawn out from me in a linear manner which doesn’t add up when the current understanding is used, atleast not to me.

        • facefault

          1. Excellent question! Neurology’s more than neurotransmitters – it also involves a lot of electrical activity. What we know about the neural correlates of consciousness thus far makes me partial to Graziano’s attention schema hypothesis, but integrated information theory is also a very interesting explanation. With that said, there’s certainly no airtight solution to the hard problem of consciousness yet.

          Let me turn the question back on you. Your hypothesis seems to presume a pre-existing outside consciousness/ observer, and that internal consciousness results from the interaction between said observer and emissions from your brain. How does that explain consciousness, rather than falling into an infinite regress of observers observing observers?

          3. Flames can quite easily be described mathematically.

          6. That’s normal empathy. Everyone can try to infer other peoples’ mental states from cues they give off. In fact, everyone does this more or less automatically.

          But it’s not actually feeling someone else’s mental state. It’s just a guess, and around people with unusual emotional responses (say, people with autism), it’s usually a wrong guess.

          It may feel like you’re directly feeling someone’s mental state. But the brain oversimplifies information for convenience all the time. For example, look at the white background around this text.

          As you probably know, white light is actually light of every visible wavelength mixed together. But you don’t see a rainbow around these words; you see white. It looks like light without any color at all – light without any wavelength at all. And that’s physically impossible! All light has wavelength.

          Every time you see white, your brain is showing you something that does not and cannot exist, instead of what’s actually there.

          It does so because that’s easier to do than showing you the real thing, showing you all the information it discarded to give you a simple and easy-to-understand summary. Because that simple summary’s more useful to you than seeing rainbows in everything white would be.

          Same thing happens every time you figure out someone else is thinking. You think what your brain concludes they’re thinking, or feel what your brain concludes they’re feeling. You don’t consciously think much about their expression, posture, tone of voice, context, etc. All that information stays subconscious.

          7. How can one consciously perceive a delay in one’s own consciousness? In reactions to something you’re aware of, sure, but in consciousness itself?

          • TLongmire

            1. The Entropic Brain is a theory that makes sense. Perhaps we are in a state of “becoming” and have the potential to “be” conscious and there is a definite division of the two.
            3. Flames are nonmathmatical that equation merely approximates how a substance transitions to a flame.
            6. Telepathy can be proven by comparing brains of people communicating, the brain of the listener synchronizes with the other brain which shouldn’t be the case because the act of speaking is different in the brain than listening right? Telepathy is the elephant in the room.
            7. I will claim that on occasion I have felt a sensation of my mind shifting outward then becoming aware that I was about to think a certain thought then actually thinking the thought. It’s nearly impossible to describe but the experience leads me to believe my mind transcends my brain but is currently entangled with it.

    • ben

      Interesting. Did you receive this from the pleiadians?

      • TLongmire

        Quantum entanglement allows for many interesting possibilities. But no I experienced that scenario and that is the best I could describe it.

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  • gcastella

    The brain is not so good with futurology.

  • Michael Kyler Johns

    XXI. What counts as an explanation of how the brain works? (and which disciplines would be needed to provide it?) Is not explainable in words but through meditation, martial arts, and isometric exercises f.y.i slowing ones heart rate down to 3 to 10 beats a minute holding one’s breath in excess of 4 minutes and to close one’s eyes in a dark room and using the imagination in such a way that it is similar to dreaming one can push out human growth hormone and other hormones in order to grow and strengthen muscles and the mind with this
    it is more understandable to ones self without words or explanation as to how the brain works?

    • Carlos Cintron Garcia

      Yeah the thing is this is a science page, not hokus pocus

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  • john gilmour

    The Human Brain in my theory, records everything we experience, and each memory is most likely stored in a Partition Like Structure, within the lobes of the brain, and comes with an application, that all a person has to do to experience a past event, is to think about it, and the mind, will provide an instantaneous sampling of the recorded memory.
    and you would have to factor in, that while recording an experience, ALL 21 or more senses, are recording, at the same time, and all senses remain electronically connected for life, there is much more recarding this subject, within my theory.

  • john gilmour

    Learning and Memory?
    most people have two memory locations short term memory, and long term memory, and I believe there may be a third memory location, which I describe as a Processing memory, which is one that collects random bits of information over long periods of time, and connecting them to appropriate previous memory particles, until enough bits of information, display, a conclusion, that something may develope, something might need further specific bits of information to complete the formulation of an idea, or theory, on a particular subject. learning would be the imbedding of the information, into the long term memory location, I have been able to accomplish this, with a specific procedure!, that I would be willing to share, if there would be any interest!

  • john gilmour

    My Theory includes the following, That the human mind, is an electronic Galaxy of it’s own, with millions of connections, to every cell of the body, brain, and organs, but may be best addressed in specific locations at a time. I believe that the Emotional Memory Archives, may be located in the frontal lobes of the brain, the specifics of emotions, include Compassion – Reason – Tolerance – Understanding, Intelligence and Wisdom. and I believe, every Assessment our mind makes, would be processed and tempered through these emotional filters, and is what may keep us on the straight and narrow?

  • john gilmour

    Abstract Ideas – I would offer the quote from
    Albert Szent Gyorgyl:
    Discovery Consists of Seeing What Everyone Else has Seen, But Thinking, What No one has Thought!
    And One of my own:
    If You are able to Comprehend the Possibility of a creation Functioning – You can make it happen!
    If you are unable to comprehend the possibility, of a creation functioning, to that person, the creation, could not work, and the creator unbalanced!

  • john gilmour

    My Theories May not be clear to those with a Medical Education, as I am unable to Communicate the Calibre of knowledge that most professionals word usage in identifying the brain, and it’s components

  • john gilmour

    John Gilmour’s Additional Theory!
    It may be Discovered that All Sound Memory Archives, will be located in the Temporal Lobes, both left and right, as everything we experience in sound, is recordedin Stereo!
    I believethe Olfactory Memory Archives, will most likely be found, in a lobe on the top surface of the Brain, as Demonstrated by Dr. Wilder Penfield, in his Heritage Minute “Dr. I Smell Toast Burning”.

  • john gilmour

    Additional Theory on Psychiatric Medication?
    It is said that a successful medication, or combination medication, that works for one patient, may not work, in another patient, with the same illness!
    And I think I may know Why that is.
    I f a medication is successful on a patient, the doctor may identify the patients genetic characteristics, such as eye colour, skin tone, and attach it to the successful medication, and when the next patient with the same genetic charachteristics, it may work in the same fashion, as it did for the previous successful patient!
    Although we all have basically the same CHemistry in our bodies, Each of us is a very specific Recipe of those chemicals, which are displayed in eye colour, skin tone, and hair colour!

  • john gilmour

    MY Theory of the Brain, includes, that observing it as a form of computer, with the lobes of the brain being referred to as the soft drive, and within each lobe, are many partitions, either in place on creation, or as needed by the minds operating system, m each archive would be a previously selected location, within which a memory recoding is placed in that partition, understanding that all aspects of any experience will be recorded and placed in different locations, such as sounds would be located, in the temporal lobe sound memory archives, with other aspects (senses) of the experience, being recorded, and placed in a variety of locations, within the brain, all seemingly previous ly selected locations, for the minds operation platforms organization, and need to have them all accessable to the
    instantaneous sampling, effect that is in play.

    Regarding theOlfactory Experience Recordins, and archiving, this operation has a very unique format, in that while breathing, the olfactory nerve, is sampling every breath we take through our nose, and sampling it against all previous samples recorded, and that may be why, when we smell smoke, our nose identifies it as a cigarette, afire of cloth , wood, food, or electrical!



No brain. No gain.

About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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