The State of Theory in Neuroscience, or How I Learned to Stop Worrying and Love the Data

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A physicist's first impressions of neuroscience.

If my initial foray into the territory of the biologists has taught me anything, its that theory in neuroscience is a very different game than that of theory in physics. Theoretical physicists are able to temporarily retreat into pure thought and calculation, minimizing communication with experimentalists, and yet still make significant scientific progress. Theoretical neuroscientists, on the other hand, are currently chained to their experimentalist brethren, doomed to empty speculation and crackpot theories if they naively strike off on their own.

Why the Physicists Can
There is a cultural myth that progress in theoretical physics is made by emaciated hermit-geniuses who go off into the woods for months, scribble equations and day-dream in solitude, and return with profound insights into Nature’s inner workings. Although this is an exaggeration, there is some truth to it. Theoretical physicists can go off into the woods and do their work (albeit usually in the company of others) and can make progress while spending a great deal of time in solitude (although most don’t). Though theorists and experimentalists do work closely with one another, theorists are capable of running off without experimentalists for months or years on end and still making scientific progress.

Albert Einstein famously popularized the Gedankenexperiment - the thought experiment meant to elucidate scientific truth based solely on previous knowledge, logic, scientific intuition, and imagination. Though Einstein did not work alone (contrary to popular belief, he had many collaborators), many of his ideas were inspired by thought experiments. For instance, his inspiration for special relativity was based on his mental simulation of chasing a beam of light. More recently, string theorists have argued that, while decades or more ahead of realizable experiments, their approaches to describing the fundamental laws of nature represent a new kind of science that places great confidence in both the ingenuity of the human mind and the beauty and symmetry of Nature (no reference here - this is just what I’ve heard on the physicist circuit).

For our purposes though, the important point is not to what degree theoretical physics can temporarily decouple from experiment; its that progress can be made by theorists at all without constantly holding hands with experimentalists.

Why is this possible? What is special about physics that allows this to occur?

First of all, this wasn’t always possible in physics. Go back to the toddler years of science when Galileo, Newton, and friends were paving the way for modern science, ask them whether they consider themselves “theorists” or “experimentalists,” and you are bound to get blank stares. The distinction between theory and experiment wasn’t made until centuries later. Galileo proposed in precise mathematical terms our modern concept of inertia and built pendulums and telescopes. Newton laid down his famous three laws and played with prisms and mirrors. In the early days of physics, theory could not stray far from experiment.

What allowed theory to periodically decouple from experiment was the establishment of a sufficient theoretical framework to begin with.

The Gedankenexperiment requires solidly tested laws from which to launch intuitive explorations. Galileo and Newton had no such thing. They had to stick very close to Nature and experiments because at that time, we knew very little about Nature. Einstein, on the other hand, had a little more going for him. He had Newtonian mechanics and Maxwell’s electromagnetic theory upon which to base his dreams about chasing beams of light. He didn’t have to actually try to chase a beam of light (which would have been a bit difficult) because he had a solid theoretical framework within to mentally simulate at least parts of the experience. In other words, a solidly tested theoretical framework can allow us to replace many basic physical experiments with thought experiments. Fast forward to today and physicists have established a much richer basis of well-tested laws, an environment that supports entire intellectual castles of theory, well-protected from the toils of experiment.

What I want to emphasize is that without an established base of theory, there can be no decoupling of theory and experiment. The modern state of theoretical physics has spoiled many scientists who tend to borrow their ideas of what theory work should look like in other fields from physics. But physics is quite different from other fields. Physics is very old, often deals with relatively simple phenomena, and has centuries worth of solidly tested theories. In other words, borrowing assumptions from modern physics is a grave mistake. For many fields, including neuroscience, it would be far better to borrow ideas about the coupling of theory and experiment from early physics.

Why the Neuroscientists Can’t
Modern neuroscience has very little theory to build upon. Sure, they’ve got the neuron doctrine, that the brain is made of individual cells, but that’s not much more than a special case of a more general law in biology. Beyond that, even the widely accepted notion that spiking neurons are the sole transmitter of information in the brain is a bit shaky. We are quickly gathering plenty of anatomical data, correlations between brain activity and behavior, and other interesting nuggets of phenomena, but broad theories to help us understand this sea of data are either non-existent or highly speculative.

Worse, its not even clear whether such theories will exist or what they will look like. While physicists simplified their game by focusing on “fundamental laws”, neuroscientists face the menacing challenge of historical accidents and messy hacks built by millions of years of evolution. Many (including myself) are banking on the existence of some basic laws that govern brain structure and dynamics, but these laws may look very different from the somewhat more “ahistorical” laws of physics.

What the Neuroscientists Can Do
So if you’re a bright-eyed, bushy-tailed, naive young physicist/mathematician who dreams of building theories of the brain, what do you do?

1. Avoid brain theories built by rogue engineers, physicists, and mathematicians who have never met a biologist.

To clarify my earlier comments, its not that brain theories don’t yet exist; its that good brain theories don’t yet exist. There are plenty of electrical engineers debuting their latest computer architecture models of the brain, computer scientists proposing their shiny new graphical models of learning, mathematicians arguing that synchronized feed-forward neural networks clearly solve the binding problem, and other rogue scientists who base their theories of the brain on their intuitions about how the brain should work rather than data about how the brain does work.[[^1]] Plato and Descartes may have had to base their theories of how the mind works on pure introspection and phenomenology, but ever since Ramon y Cajal starting poking around neural tissue, we’ve had real live data to guide our intuitions. Decades from now, we will look back on the state of theory in modern neuroscience and wonder how so much nonsense was published. No field in science today is more polluted with bunk theories and outrageous publications than neuroscience.[[^1]] If you want to understand actual brains, don’t fill your own with this drivel. [^1]: For the sake of not making too many enemies, I’ll avoid references here, but you know how to use Google.

2. Form tight collaborations with experimentalists (and maybe even do a few experiments yourself).

There is room for theory in neuroscience - theory tightly coupled to ongoing experiments. Find people with patch clamps and MRI machines. Understand what they do and how they do it. Propose new experiments and try to help explain the results of old ones. The interesting and achievable projects in theoretical neuroscience of today are not the grand challenges such as explaining the hard problem of consciousness; they are explaining the tiny anomalies in experimental data that make you pause for a moment and scratch your head. Why does the distribution of synaptic strengths in rat visual cortex follow a lognormal distribution? Why does it consistently seem that roughly 90% of neurons are inactive? Why does ferret visual cortex activity rate and variance seem to rise throughout early development, peak, and then decline in maturation? These are the types of questions we need to tackle first before we can explain consciousness, thought, love, and all of that fun stuff. As much as I look forward to the possibility of understanding the brain well enough to support genuine Gedankenexperiment-style theory work, we’re not there yet. Now is the time for theoretical neuroscientists to imitate the physicists of Renaissance Europe, not those of Princeton and Waterloo. In other words, either get your hands dirty with experiments or make friends with someone who does.

Either way, don’t stray far from the data.