alikwidge.bsky.social
Neural engineer, stealth mode neuro-entrepreneur, interventional psychiatrist, sometimes neuroscientist, dad. Making brains work better.
https://www.tnelab.org
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Intriguining given the argument that MOR is involved in suicidality and the effects of ketamine, and I see a lot of folks using ketamine to deal with ACEs...
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Loved this, thank you for the reference.
I think you saw our STM paper that dropped 2 weeks ago that shows DBS affecting evidence accumulation in the DDM.
Sure feels like these two are related under the hood.
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www.biorxiv.org/content/10.1... is 90% of the same content
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You've seen previews before at ACNP, but this time we explain the math!
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Then a full year of refining results, doing human replications, fixing bugs, and carving a heap of raw data into a paper. Plus another year of peer review to give you this early Solstice present in 2024. So that's what translational science takes! 12/12
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It also took 8 years. Adriano Reimer, the first author, started the first pilots in 2016. We had the model by 2018 when we moved, but it took till 2022 to have all of the cohorts and controls run (damn pandemic) and till 2022 to figure out how to do DDM in the presence of learning (Evan again). 11/
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It also highlights the power of the RDoCian approach we argued for in pubmed.ncbi.nlm.nih.gov/37415081/ : there aren't many clinical effects that look the same in humans and rats. This does. It's the closest I know to a "model of" in psychiatry. 10/
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AND, you could start to opto dissect what individual components do, why the heck 130 Hz matters, and all the "why does DBS even work???" stuff that's bothered me for years.
So that's why rats, but because it's reverse translation, we can really hope what we learn will matter to people. 9/
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AND, if you happen to have a model for how you could optimize DBS for cognition (like in iopscience.iop.org/article/10.1...), now you have an animal system where you can test your optimizers and make sure they work before clinical trials. 8/
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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 pubmed.ncbi.nlm.nih.gov/30948727/ . 7/
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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/
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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/
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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/
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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/
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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/
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And you wonder how Freud made psychoanalysis work.
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One maybe-reason for the weird: balanced M/F cohort. Follow on analyses suggest major sex diffs in encoding. Most theta/gamma findings are in males only.
But the freezing thing is almost certainly driven by how noisy freezing scores are. That scares me given how much everyone relies on it.
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I mean, we collaborate now, we could split a pan. I'm definitely making this recipe as part of my celebration of Pumpkin Spice Season.
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I tell my students that the job of the PI is to find ways to do the research in a system that doesn't want us to.
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Wow do I feel seen right now. And the "you won't be able to hire yourself" is something I've been saying for years to folks starting their own labs.