Out today: cross-species improvement of cognitive flexibility www.science.org/doi/10.1126/... The TLDR: remember when we improved human cognition with deep brain stimulation? (pubmed.ncbi.nlm.nih.gov/34725508/) Well, now we did it in rats, and it works the same! Specifically... 1/ - ThreadSky

alikwidge.bsky.social • 71 days ago

Out today: cross-species improvement of cognitive flexibility
https://www.science.org/doi/10.1126/scitranslmed.adp1723

The TLDR: remember when we improved human cognition with deep brain stimulation? (https://pubmed.ncbi.nlm.nih.gov/34725508/)
Well, now we did it in rats, and it works the same!
Specifically... 1/

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alikwidge.bsky.social•71 days ago

In humans, the improvement is an RT decrease on a conflict task WITHOUT more errors, BUT, it only happens if you hit a "sweet spot" in the mid-dorsal capsule.
In rats, it's the same thing in Set-Shifting, complete with the anatomic pattern.
But if it already works in people, why bother with rats? 2/

alikwidge.bsky.social•71 days ago

Because you can't make humans perform the same task with stim on and off for weeks at a time to get tens of thousands of trials and do extensive computational modeling.
But you can in rats, so we (mainly Evan) did, and that tells us a cognitive mechanism. 3/

alikwidge.bsky.social•71 days ago

It's easy to get shorter RTs in a drift-diffusion model, just tighten the bounds. Only problem is, that'll give you more errors... unless you ALSO raise the drift rate. Which is what actually happens in rats, and basically in humans (slight differences due to task differences). 4/

alikwidge.bsky.social•71 days ago

But we couldn't have found that human result without the rat data to arbitrate between models, so that's reason 1 for needing the reverse translation.
Reason 2 is that humans object if you slice their brains for c-fos to understand where those computational changes happen. 5/

alikwidge.bsky.social•71 days ago

Unsurprisingly, it's in PFC, but differentially -- bounds more in PL, drift rate more in IL. That's clinically interesting -- it suggests that to make DBS work, you need to modulate multiple PFC-thalamic-striatal sub-circuits. There's not one magic button -- it's a broad effect across PFC. 6/

alikwidge.bsky.social•71 days ago

That matches what we know clinically. For instance, think about @andreashorn.org 's sweet spots -- they are right in the middle of the capsule where the electric field can hit projections of multiple areas. We also saw widespread EEG changes in https://pubmed.ncbi.nlm.nih.gov/30948727/ . 7/

jaredwyoung.bsky.social•71 days ago

Very cool Alik, can't wait to read in-depth!

alikwidge.bsky.social•70 days ago

You've seen previews before at ACNP, but this time we explain the math!

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