Nicole RustFeb 8, 2023

On Grand Plans in brain research:

The Grand Plan for brain research might be stated as 'figure out stuff, then do useful stuff like fixing' (i.e basic > translational research). But that's pretty vague.

A more concrete plan is called molecular medicine. So central, it's even summarized in the Introductory textbook Neuroscience (Fig 22.2): Identify a genetic mutation that causes a disorder >>> drug treatment. That hasn't worked out so well and many doubt that genes are the right level to jump in. There's a parallel TL; DR in which genes are replaced with noninvasive measures of brain activity (like fMRI), but that has also been problematic and many doubt that will work either. (Of course variants of both are being pushed and pursued.)

More abstractly, if molecular medicine was a Plan, we might say that we've returned to the drawing board with a MetaPlan: develop the knowledge and tech for new measures >> pinpoint the causes of dysfunction >>> treatments. In other words, the hunt is on for new understanding & tech to create measures. Once those are developed, it becomes a plan that we can summarize in textbooks once again.

Agree? Do you have a different concept of the Grand Plan for brain research?

Show threadHB Lab
@NicoleCRust how come that every single link works well yet the whole chain doesn't...
Feb 10, 2023 at 1:22pmWeb
Show threadNicole RustFeb 10, 2023

@jiahongbo

Interesting point. I think we can point to the links that are broken, but they are different links for different disorders.

For psychiatric disorders, there's a lot of evidence that the first link is broken. Schizophrenia, Autism, Depression - they are linked to variation in hundreds of genes (not one). That's also true about fMRI measured brain activity: we cannot link it to psychiatric disease for individuals (so we don't have anything to target down the chain). We do not any have biomarkers for these disorders.

For some other neurological disorders, the broken links are further down the chain. Huntington's is a single gene mutation we've known about for 30 years but we don't have a drug to treat it. A drug was developed in a mouse model, but it did not work in humans (last link).

Alzheimer's is more complex to map on this figure. We have a handful of genes but it's clearly also some interaction with the environment. We have biomarkers (amyloid plaques and tau tangles) and we've developed drugs around them. Those drugs do the biological thing they were supposed to do, but they don't slow cognitive decline. The relationship between the biomarkers and the causes of Alzheimer's is in question.