The Sherlock Holmes novel The Hound of the Baskervilles features the great Grimpen Mire, a treacherous marsh in Dartmoor, England. Holmes’ protagonist, the naturalist Stapleton, knows where the few secure footholds are, allowing him to cross the mire and reach the hills with rare plants and butterflies, but he warns Dr. Watson that a false step can be fatal, the bog inexorably consuming the unsuspecting traveller. Trying to unravel the complexities of the brain is a bit like crossing the great Grimpen Mire: one needs to know where the secure stepping-stones are, and a false step can mean sinking into a morass. As we enter the era of Big Brain Science projects, it is important to know where the next firm foothold is.
As a goal worthy of a multi-billion dollar brain project, we have now been offered a motto that is nearly as rousing as “climb every mountain”: “record every action potential from every neuron.” According to recent reporting in the New York Times, this goal, proclaimed in a paper published in 2012, will be the basis of a decade-long “Brain Activity Map” project. Not content with a goal as lofty as this in worms, flies and mice, the press reports imply (and the authors also speculate) that these technologies will be used for comprehensive spike recordings in the human brain, generating a “Brain Activity Map” that will provide the answers to Alzheimers and Schizophrenia and lead us out of the “impenetrable jungles of the brain” that hapless neuroscientists have wandered over the past century.
Neuroscience is most certainly in need of integration, and brain research will without doubt benefit from the communal excitement and scaled up funding associated with a Big Brain Initiative. However, success will depend on setting the right goals and guarding against irrational exuberance. Successful big science projects are engineering projects with clear, technically feasible goals: setting a human on the moon, sequencing the Human Genome, finding the Higgs Boson. The technologies proposed in the paper under discussion may or may not be feasible in a given species (they will not be feasible in the normal human brain, since the methods involved are invasive and require that the skull be surgically opened). However, technology development is notoriously difficult to predict, and may carry unforeseen benefits. What we really need to understand is whether the overall goal is meaningful.
The fundamental problem with the goal of measuring every spike of every neuron is one of conceptual incoherence: the proposal does not stand up to theoretical scrutiny.
According to the paper, the reason we don’t yet understand how the brain works is that brain function depends on so-called “emergent properties” and that these “emergent properties” can only be studied by recording all spikes from all neurons in the brain. “Emergent property” is a troublesome phrase and it is not exactly clear what it means, but the authors also point to correlated or collective behavior of neurons, and to phenomena from physics in which collective behavior plays a role. Further, the authors imply that this correlated or collective behavior cannot be deduced from other levels of observation (including the circuitry), hence the imperative need for the “measure every spike” project.
What is wrong with this picture? First, brains do not exist in isolation. Spikes are driven by two sources: the intrinsic dynamics of the neuronal network, and external stimuli. Even if one recorded all spikes from all neurons (and for the entire life span of the organism), to make any sense of the data one would have to simultaneously record all external stimuli, and all aspects of behavior. It gets worse: there will be individual variation among animals, and each animal will have a different environmental history. The “comprehensive” measurement exercise would extend ad infinitum.