Elusive Cures: Why Neuroscience Hasn’t Solved Brain Disorders―and How We Can Change That

by Professor Nicole C. Rust

A neuroscientist’s bold proposal for tackling one of the greatest challenges of our time—brain and mental illnesses

Brain research has been accelerating rapidly in recent decades, but the translation of our many discoveries into treatments and cures for brain disorders has not happened as many expected. We do not have cures for the vast majority of brain illnesses, from Alzheimer’s to depression, and many medications we do have to treat the brain are derived from drugs produced in the 1950s—before we knew much about the brain at all. Tackling brain disorders is clearly one of the biggest challenges facing humanity today. What will it take to overcome it? Nicole Rust takes readers along on her personal journey to answer this question.

Drawing on her decades of experience on the front lines of neuroscience research, Rust reflects on how far we have come in our quest to unlock the secrets of the brain and what remains to be discovered. She shows us that treating a brain disorder is more like redirecting a hurricane than fixing a domino chain of cause and effect, arguing that only once we embrace the idea of the brain as a complex system do we have any hope of finding cures. Rust profiles the pioneering ideas about the brain that are driving research at the cutting edge to illuminate exactly how much we know about disorders such as Parkinson’s, epilepsy, addiction, schizophrenia, and anxiety—and what it will take to eradicate these scourges.

Elusive Cures sheds light on one of the most daunting challenges ever confronted by science while offering hope for revolutionary new treatments and cures for the brain.

Genres: Science, Nonfiction, Brain, Biology, Psychology, Neuroscience, Health

296 pages, Hardcover

Published June 10, 2025

About the author

Nicole C. Rust is an author, professor and scientist at the University of Pennsylvania. Her research focuses on understanding our remarkable ability to remember the things we’ve seen (“memory”) and what drives the mysterious feeling we call “mood”. As a complement to this foundational research, she works to develop new therapies to treat memory and mood disorders.

Rust is the recipient of numerous awards, including the Troland Award from the National Academy of Sciences. She serves as a contributing editor at The Transmitter, a leading brain research news magazine. Rust is the author of the book Elusive Cures: Why Neuroscience Hasn’t Solved Brain Disorders — and How We Can Change That. In it, she argues that treating a brain disorder is more like redirecting a hurricane than fixing a domino chain of cause and effect, and that only once we embrace the idea of the brain as a complex system will we have any hope of improving treatments and cures for brain and mental illness.

Reviews

[Cav · Rating 5 out of 5]

"I was inspired to write this book to help individuals who are afflicted with some type of brain or mental dysfunction, or have a loved one who is. I am among you, and I am empathetic..."

Elusive Cures was an excellent in-depth look into the complicated machinations of the human brain. The brain has been described as the most complex system in the known universe. As Bob Moawad once said “the human mind is the fastest, coolest, most compact and efficient computer ever produced in large quantities by unskilled labor.” (I always got a chuckle out of that one)

Author Nicole C. Rust is an American neuroscientist, psychologist, and a Professor of Psychology at the University of Pennsylvania. She studies visual perception, visual recognition memory, and mood (psychology).

Nicole C. Rust :


Rust has a good writing style that shouldn't struggle to hold the finicky reader's attention. The book gets off to a good start, with a well-written introduction. The author drops the quote above near the start of the book, and it continues:

"..I acknowledge that there are complexities around whether and when we should consider some conditions as “dysfunction” as opposed to a type of neurodiversity that society has wrongly become intolerant to—cases of autism, attention deficit hyperactivity disorder, and depression are all examples. That said, for each of these conditions, a subset of diagnosed individuals suffer in ways that can benefit from treatment. For those individuals, when our existing treatments fall short, we need better ways to help them. With this empathetic spirit, I use the terms “dysfunction” and “disorder” to refer to the conditions of individuals who need better solutions than the ones we can offer them today."

The writing in the book is a detailed and technical examination of complex neurobiology and neurochemistry. I found lots of thought-provoking writing that I have not heard elsewhere here. Well done! I will caution potential readers of this book that they should probably have a decent level of scientific literacy before starting this one, in order to follow the writing here. The author uses a lot of scientific jargon as well as concepts that will likely be unfamiliar to the layperson.

In this short quote, she talks about her credentials and the aim of the book:

"I am a neuroscientist, and I have been engaged in brain research for over two decades. For a long time, I’ve been convinced that I have the best of all possible jobs: I get paid to think up new questions about how the brain works and answer them. A large part of what inspires my research is my intense curiosity about how the brain gives rise to the mind, and to ourselves. To answer these questions, I focus on memory. I investigate questions like: When we have the experience of remembering that we’ve seen something before, what is happening in our brains? How do our brains manage to remember so much? And how do our brains curate what we remember and forget?
My work is not driven just by curiosity; I believe that a foundational understanding of how memory works will contribute to future treatments and cures for memory dysfunction, including age-related dementias such as Alzheimer’s. In fact, part of my research program focuses on transforming what we’ve learned about memory into the earliest stages of developing a new treatment for memory impairment. Ours is but one example of what is known as the bench to bedside approach, where fundamental research discoveries are the first step toward developing new clinical treatments."

Her main thesis here is that the brain is not a "linear domino chain," but rather a "complex, adaptive, dynamical system." As mentioned at the start of this review, she says that the brain is the most complicated system in the known universe. In dealing with such complex systems, crunching local and systemic numbers becomes prohibitive. Instead, chaos theory applies. However, chaotic systems are extremely difficult to forecast and even harder to control. She expands in this bit of writing:

"Hands down, the most profound and important insight I’ve had while writing this book is that the end goal of treating brain dysfunction amounts to one of the most formidable of all possible challenges: controlling a complex system. Not in the creepy or cartoonish sense of “mind control,” but in the sense that treatments require shifting the brain from an unhealthy to a healthier state. This challenge is so formidable that there are questions about whether it can even be done in principle (much less in practice). The answer depends on exactly what type of complex system we’re dealing with.
To illustrate, let’s look at what happened when we tried to control another complex system: the weather. Today, we don’t try to influence the paths of hurricanes. Why not? It’s not because we haven’t tried. Often forgotten about the history of weather research is that we did try, only to realize that it probably won’t work. Thus, we need to ask ourselves: What makes us think that the brain will be any different? After all, an epileptic seizure or psychosis might be likened to a tornado or a hurricane insofar as it’s a complex system gone awry. Under what conditions can we effectively control a complex system?"

Some more of what's covered here includes:
• Alzheimer's
• Cognitive Behavioural Therapy
• Electroconvulsive therapy (ECT)
• Phenylketonuria (PKU)
• Cystic Fibrosis
• Capgras Syndrome
• Waddington’s epigenetic landscape (some very interesting writing here)
• Emotions
• Emergance; complexity
• Opioid drugs
• Brain stimulation
• Seizures; auras; Dyostyevky
• Cancer drugs; drug resistance
• Parkinson’s disease
• Strokes; recovery
• Psychedelics
• A "Grand Plan for Brain Research"

I will add a small gripe here. In the book, she says that there is no therapy that can slow the rate of progression of Parkinson's disease. As someone with a close relative who suffers from PD, this runs contrary to what I have read elsewhere. She talks about pharmaceutical interventions, but doesn't mention the potential benefits that regular vigorous exercise can provide. A cursory Google search yields a bunch of studies that seem to show that regular vigorous exercise can potentially help slow, or even reverse some of the decline associated with the disease. So, for anyone reading this who may have (or know someone affected by) PD, GET AFTER IT! I'm rooting for you! 💪

********************

I really enjoyed Elusive Cures. It was a thought-provoking read full of super interesting material.
Despite my minor complaint above, I would easily recommend it.
5 stars and a spot on my favorites shelf.

[Eva · Rating 5 out of 5]

Restored my optimism that dynamical systems approaches to neuroscience (like what my lab does) are pointing us in the right direction. Approachable and honest. 4.5 stars
(Note: audiobook, not hardcover)

[Tanya · Rating 4 out of 5]

very sciencey but great rec jake

[Hawk · Rating 4 out of 5]

Pretty good! Really gave me some insight on the intersection of complex systems and neuroscience and how the present research approach can be a form of “stamp collecting”,. Felt a bit contrived and droning at times though. Full review coming soon!

[Mateo · Rating 4 out of 5]

This is an excellent, empathetic, and very readable introduction to the current state of researching with the goal of curing brain disorders, from the psychiatric (ex. schizophrenia) to the neurological (ex. Alzheimer’s). The topics are selected well and provide a pretty clear framework for how to think about the way the brain is being studied. Everything is super organized and clear, with many past examples from other fields cited to describe how positive changes in the way people thought about scientific questions can be effected in neuroscience. The explanations of recent discoveries in clinical and basic neuroscience are also very clear, and gave me a lot more to think about within the context of brain disorders (despite my working directly in this field). I also enjoyed the discussions on metrics, causality, and translation.

Once the main point, which emphasizes a more flexible framework for studying the brain, is explained, it does leave open a lot of room for thought. The author does admit that studying the brain with this perspective is a tall order and difficult to prospectively describe and that discussing new approaches in a collaborative setting could be very time-consuming. The main point is repeated a lot of times toward the end, but the lack of clear details on implementing (not a fault) and the fact that a lot of the possible success of this framework is contingent on a bunch of scientists doing something different may not be the most satisfying conclusion to the book for a layman. More emphasis on how this changed the author’s view on neuroscience research w.r.t. brain disorders and how understanding and empathetic this perspective actually is would make it more relatable. This would be a superb blog post on a science forum (and luckily existing neuro- and other scientists are a huge portion of the intended book audience) but relating it back to why this matters for the person reading would make it better as a book. For the scientists, more details regarding the modeling and scientific approaches that utilized ideas from complex systems analysis would be helpful (still mulling over the results and implications from Mante et al. 2013!). While the science/math is not demanding, the book would benefit from pivoting more toward scientists or more toward laypeople, who I think may struggle not with the technical details but rather the “okay and how does this affect me and what can I do about it.”

The tone is also decent. As far as accessible science writing goes, things can be a bit more engaging.

Overall, the book is very detailed and very clear, and anyone who wants to know more about how neuroscience research can pivot toward treating brain disorders should give this a read.

[Hannah · Rating 5 out of 5]

Neuroscientist here! (Full disclosure: the author did some lectures in one of my graduate courses.) I loved this book. It challenges the way I learned to conceive of the brain (with my PhD on behavioral genetics) and recontextualised the way I think about polygenetic / multifactorial brain disorders. In an academic system that rewards hyper-specialization, Rust goes broad with this book, illustrating how applying the idea of complex systems is useful for understanding brain function and dysfunction. She makes the case that this is the next paradigm shift that the field needs, moving away from a "domino chain" model of causality to imagining the brain as something more like the weather, or an ecosystem.

This book is also going to change the way I teach my undergraduate lower-level neuro courses. In these courses, I tend to teach "domino chain" logic because it's just so much easier for students to grasp than a complex, multi-nodal system with interlocking feedback loops-- which Rust convincingly writes is what the brain IS, at many levels. But now I'm going to bring in that complexity earlier, because Rust makes a convincing argument that complexity is a fundamental feature of the brain. As a more cellular / molecular / genetics-inclined neuroscientist, do I think we maybe got a little short shrift here? Perhaps a tad. After all, as Rust points out, cell biologists have been thinking of intracellular signaling and metabolic networks as complex systems for a while now. And I wish she'd have drawn out more the fact that neurons and glia ARE CELLS, that the brain is a billion-cell matryoshka doll of complex systems. As someone who studies a rare monogenetic brain disorder, do I think the domino chain model still has a place in the world? Yes. But for psychiatric and neurodegenerative disease, with their wildly entangled cause-effect-cause-effect-causes, Rust has convinced me that a complex systems paradigm has a lot to give the field.

[Jacob · Rating 5 out of 5]

This was a brilliant book that really shaped the way I think about the brain. Rust asks why all of the neuroscience advances in recent decades — fMRI studies, genetics, brain stimulation — have not always translated to new treatments.

For example, many new medications like antidepressants are small adjustments to drugs that have been around for decades, and many of these were discovered serendipitously. Other drugs like lecanemab were created to reduce amyloid plaques, a common occurrence for Alzheimer’s patients, but do not improve symptoms as much as expected because these plaques appear to be a symptom of the underlying issue rather than the cause.

Her hypothesis is that our mental model of brain treatments needs to be reconsidered. First, we do not actually have standardized ways of quantifying things like depression and anxiety right now, relying on batteries of tests. She likened this to the quest to quantify temperature which I thought was a fascinating story.

More importantly, we often follow the broken domino theory where we assume causal pathways move in one direction and medications need to fix the broken domino in the chain. In fact, the brain is a complex, adaptive system where causality flows in many directions. The system is often at the knife’s edge of order and chaos and can fall into one or the other in unpredictable ways. To correct course, we need to guide the entire system back rather than fixing a single domino. We may be better off using examples like weather systems and ecology to understand the brain. I thought this was a wonderful analogy and learned so much from this book. Will continue to share with friends and family!

[Anika · Rating 5 out of 5]

I really enjoyed this book. Rust makes a great effort to make this book digestible for the interested and motivated layfolk by using (but not relying exclusively on) metaphor, repetition of core concepts, and short histories of various treatments. I thought it was mostly successful in my case, but I wished that I also had a physical copy and not just the audiobook as there were some parts I really needed to revisit several times to understand.

I also loved that the book starts out with some reassurance for the reader that ultimately Rust is hopeful about where neuroscience is headed and that the ideas shared in this book capture promising development in finding real results for people afflicted with some of these brain disorders.

It didn't take much to convince me of the need for understanding the brain as a complex system, but what really struck me upon reflection is how integrated a domino-chain perspective of the brain is into colloquial language and common understanding. This seems particularly true in the case of psychological disorders. I was glad to hear treatment resistant depression acknowledged and learn more about the most up-to-date understandings of schizophrenia and its complex origins.

For me, in a family dealing with the reality of Alzheimer's I found this book helpful as a tool for understanding the treatment development and grasping onto some hope that if/when I myself am likely dealing with dementia in 40 or 50 years there might be some more effective medicines and treatments.

[Anne · Rating 3 out of 5]

Well written book about the limits of reductionistic neuroscience. After having seen Rust speak about the field’s grand plan at the 2024 conference (on youtube), the book mostly added some nice examples.

Fundamentally, however, I think Rust does not take her systems thinking far enough - she remains focused on the individual brain. I would love to see where her thinking is in a few years, especially given that for mental health problems like depression, I believe that the solutions and interventions lie predominantly at the levels of political change, rather than individual therapy (even when based on complexity-guided systems neuroscience).

[Kyle Wright · Rating 4 out of 5]

I don't often listen to Sean Carroll's podcast, but I recently listened to the episode with Dr. Rust and enjoyed it, so I decided to go ahead and listen to her audiobook. Pretty good. A bit repetitive, probably could've been a decent bit shorter, but the content and presentation is well-constructed. Lately, I've been thinking a lot about complex nonlinear systems, and I figured it might be fun to hear how other fields are applying ideas from control theory and attractor dynamics to very different kinds of networks. Still a bit early in the process, it seems. Fair enough!

[Diane · Rating 5 out of 5]

I learned a lot from this book. There's a gap between what scientists have been learning about the brain and treatments for brain and mental disorders and the book tries to describe why. The science is complicated but the author (who is a scientist) makes it all very accessible and engaging. I liked that she described it as a personal journey to figure these things out for herself. I left feeling optimistic.

[Julia Gorman · Rating 5 out of 5]

It’s so hard to write a good book about science because you have to toe the thin line between giving high level understanding to a broad audience and going into the niche details for the scientists with the background who want to know the nitty gritty. This book definitely leans heavy on the details, which scratched an itch for me. I really enjoyed this book and have long been a fan of Rust’s work so I was really excited to read this.

[Rebecca · Rating 4 out of 5]

Very clear, even the genetics parts were generally accessible. It’s interesting to read a book at the cusp of a scientific paradigm shift, that’s more a proposal of how to do science than about a synthesis of results. It’s an empirical question to what extent this paradigm shift ends up being “correct” or helpful!

[Il Yong Jung · Rating 3 out of 5]

Too hard for me as a layman to understand the complexity and path as explained by the author. Also seemed a bit repetitive. Perhaps someone who is more professionally aligned would better appreciate this book.

[Paula · Rating 4 out of 5]

Buena recapitulación pero no añade nada nuevo

[helyinyang]

read for book club with lab

[Helia Naderi · Rating 4 out of 5]

Extra reading on this topic: https://www.thetransmitter.org/drug-d...

Going into this book expect many tangents, expect doing some research to understand those tangents, expect some mental gymnastics to understand the ultimate relevance of those tangents. And this is because the book strives to cover way more than it can fit in less than 300 pages.

Although reading this book was a 3-star experience it gave me a lens to view the field through a wider more practical perspective so I’m grateful. I’m really counting on the reread to be more illuminating!