On the Grand Plan for brain and mind research

 It's a bit atypical, so let me unpack it.

But before I do, let me begin with an introduction. I'm a brain researcher, and I've been one for quite a while now (decades). Of that ilk, I'm the flavor often called "basic" or "foundational." Brain and mind research is organized around the premise that benefits to society (like treating brain dysfunction or building brain-like Artificial Intelligence) follow from a nuts-and-bolts understanding of how the healthy brain and mind operates. In the case of dysfunction, it's often captured in the phrase "bench to bedside," which refers to the idea that foundational biomedical discoveries (at the proverbial research bench) are a first step toward creating new treatments for disease. In that phrase, I'm a card-carrying member of the "bench."

A few years ago, I began to wonder: Why have we been learning so much about the brain and mind for so many decades, but our ability to treat its dysfunction has been so frustrated? Especially when held up against the exploding progress in building brain-like AI? There are important exceptions, but on the whole, the "bench" seemingly has been progressing at a rapid clip, whereas the "to bedside" has been a bit stuck — particularly in our attempts to understand and treat neurodegenerative disorders (like Alzheimer's disease) and neuropsychiatric disorders (like depression). As one example, consider this haunting quote from Tom Insel, the director of the US National Institutes of Health from 2002–2015:

"I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that, I realize that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs—I think $20 billion—I don’t think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness. I hold myself accountable for that."

I'm one of those "cool scientists." You may be too. The big question is: Why aren't we moving the needle? Are we on the right track, and there's just an immense amount to figure out? Or might it be because we've been thinking about the brain and mind in the wrong way?

That Why? conversation is the one I want to have with you. It informs what I affectionally call the Grand Plan — a description, in broad strokes, of how we plan to get from where we are to societal benefits. And because the benefit that appears to be the most stuck is the creation of treatments for brain dysfunction, I'd like to focus there. In response, one might quip that the Grand Plan must be something like:

Step 1) Figure out the brain and mind,

Step 2) Figure out the causes of brain and mind dysfunction,

Step 3) Create treatments, preventions, and cures.

But that's a sketch, not a plan! What's the actual plan to accomplish these things? What lessons can we draw from history? To the degree that it is working, what has contributed to its success? To the degree that it has been stuck, can we see why? And if we think it is stuck, how do we intend to get it unstuck?

Circling back to a few years ago, it was then that I first realized I could not find the Grand Plan explicitly written down anywhere. Moreover, I couldn't write one down myself (at least one that I was optimistic about), and that fact put me into an existential tailspin. I'm a brain researcher, and if I cannot articulate the Grand Plan, how can I contribute to implementing it? That spin inspired me to spend all the time I could spare for the better part of two years trying to figure it out. To do so, I sifted through an immense literature focused on brain and mind research of all types, as well as the history and philosophy of science. That journey was illuminating and transformative. Zooming out to 40,000 feet helped me see how all the dots connect, and I want to pass along what I've learned so you can see it too. Personally, I left the exercise with two big impressions.

• First, the "bench" arm of brain and mind research is in the midst of shifting in a meaningful way (one that I didn't recognize before the journey), and I'm optimistic that it will help get the "bedside" arm unstuck.

• Second, brain and mind research could benefit from researchers talking more about the Grand Plan.

I'm walking away from the experience committed to helping with both.

As I work to organize these discussions, I want to emphasize two things. First, the Grand Plan for brain and mind research will never be the genius of any member or even a handful; it will always be the genius of a large community (of which I am but one member). As such, I regard my role in these discussions first and foremost as a curator. My goal is to help sift through an immense amount of material to channel the ethos of our era and spell out the emerging intellectual framework driving brain and mind research forward. (That's what I mean by "atypical" up there at the top — you don't often see researchers giving talks or writing papers of this ilk, which is more akin to the role of a science writer or journalist). I'm honored to contribute in this way because I think it's so important. As I do, please know that while I have not abandoned research, when you hear me talk about the Grand Plan, you won't hear much about my own work. Instead, you'll hear me weave together the threads of many (many!) others at a very high level.

The second thing I want to emphasize is that the goal of discussing the Grand Plan is not to arrive at a singular prescriptive way of doing things that every brain and mind researcher must adhere to. In fact, there are good reasons to build pluralism into the Grand Plan — the notion that we should approach any difficult problem in multiple ways. Moreover, having the discussion about treatments as the end-goal does not imply that we should do away with curiosity-driven research; "basic" research remains absolutely crucial for laying the foundations we need. Instead, the goal here is to zoom out and glimpse how everything connects. From there, we can infer the challenges we're up against and what makes them so formidable. How do we conceptualize what those problems are? What do we think might be the most promising solutions? What types of nuts-and-bolts understanding do we most likely need if our end-goal is to treat brain and mind dysfunction? If that description is too vague, it might be helpful to read an example of the type of thing I'm thinking about, here.

With all that unpacked, I'm excited to discuss the Grand Plan for brain and mind research with you! And I'm grateful to the organizers of the Cognitive Computational Neuroscience (CCN) meeting (August 6-9, 2024, Boston) for providing an opportunity for us to do so.

In the longer term, I hope there will be many other discussions of this type, in many venues (including and without me). I'm grateful to the colleagues that have participated in these discussions thus far. In addition to CCN, I have a handful of other discussions in the queue, including ones that will appear in The Transmitter. I've also written down a much more linear version of the (highly nonlinear) path I traversed these last few years as a book in hopes that it will make it easier for others to sift through it all. My best current guess is that it will publish sometime in Spring 2025 (Working title: Rethinking brain dysfunction; under contract, Princeton University Press).

No doubt there will be other opportunities for us to discuss the Grand Plan. I'm very much looking forward to it.

Nicole Rust

March 6, 2024