The tale of the neuroscientists and the computer: why mechanistic theory matters.

INTRODUCTION A little over a decade ago, a biologist asked the question “Can a biologist fix a radio?” (Lazebnik, 2002). That question framed an amusing yet profound discussion of which methods are most appropriate to understand the inner workings of a system, such as a radio. For the engineer, the answer is straightforward: you trace out the transistors, resistors, capacitors etc., and then draw an electrical circuit diagram. At that point you have understood how the radio works and have sufficient information to reproduce its function. For the biologist, as Lazebnik suggests, the answer is more complicated. You first get a hundred radios, snip out one transistor in each, and observe what happens. Perhaps the radio will make a peculiar buzzing noise that is statistically significant across the population of radios, which indicates that the transistor is necessary to make the sound normal. Or perhaps we should snip out a resistor, and then homogenize it to find out the relative composition of silicon, carbon, etc. We might find that certain compositions correlate with louder volumes, for example, or that if we modify the composition, the radio volume decreases. In the end, we might draw a kind of neat box-and-arrow diagram, in which the antenna feeds to the circuit board, and the circuit board feeds to the speaker, and the microphone feeds to the recording circuit, and so on, based on these empirical studies. The only problem is that this does not actually show how the radio works, at least not in any way that would allow us to reproduce the function of the radio given the diagram. As Lazebnik argues, even though we could multiply experiments to add pieces of the diagram, we still won’t really understand how the radio works. To paraphrase Feynmann, if we cannot recreate it, then perhaps we have not understood it (Hawking, 2001; Eliasmith and Trujillo, 2014). Lazebnik’s argument should not be construed to disparage biological research in general. There are abundant examples of howmolecular biology has led to breakthroughs, including many if not all of the pharmaceuticals currently on the market. Likewise, research in psychology has provided countless insights that have led to useful interventions, for instance in cognitive behavioral therapy (Rothbaum et al., 2000). These are valuable ends in and of themselves. Still, are we missing greater breakthroughs by not asking the right questions that would illuminate the larger picture? Within the fields of systems, cognitive, and behavioral neuroscience in particular, I fear we are in danger of losing the meaning of the Question “how does it work?” As the saying goes, if you have a hammer, everything starts to look like a nail. Having been trained in engineering as well as neuroscience and psychology, I find all of the methods of these disciplines useful. Still, many researchers are especially welltrained in psychology, and so the research questions focus predominantly on understanding which brain regions carry out which psychological or cognitive functions, following the established paradigms of psychological research. This has resulted in the question being often reframed as “what brain regions are active during what psychological processes,” or the more sophisticated “what networks are active,” instead of “whatmechanisms are necessary to reproduce the essential cognitive functions and activity patterns in the system.” To illustrate the significance of this difference, consider a computer (Figure 1). How does it work?