P.P.S. As far as treatments go, my prediction would be that varenicline would be most effective in treatment individuals with neuroinflammation in the dorsal striatum in particular, based on prior work showing that acetylcholine in the dorsal striatum is necessary for cognitive flexibility

We have recently back-translated a task from humans to rats and mice (called value modulated attentional capture) that is associated with transdiagnostic compulsivity, and we are finding really interesting effects of neuroinflammation in dorsal/ventral striatum on that too. Stay tuned!

environmental circumstances (e.g. sometimes it is underscored by enhanced cognitive control, other times it results from increased sensitivity to cues). This is interesting as it shows that compulsivity is complex and multi-faceted, which could be why treatments work for some and not others. 4/4

such that these individuals might have distinct cognitive processes underlying their compulsivity. Second, for those with neuroinflammation in both regions it could mean that the source of their compulsivity is multi-factorial and changes depending on the 3/4

goal-directed control, whereas in the ventral striatum, neuroinflammation caused excessive sensitivity to cues. This is interesting for a couple of reasons, first because different individuals have different distributions of neuroinflammation in their striatum 2/4

Probably the thing that is most exciting to me is the finding that, even within the striatum, there is heterogeneity in the behavioural consequences of neuroinflammation in different regions. That is, neuroinflammation in the dorsal striatum caused excessive 1/4

Thank you! I would love to think so. Anti-inflammatories, cholinergic agonists (e.g. champix/varenicline) with anti-inflammatory properties are two of the ideas we are going to try in the lab. Also interested in exercise, sleep, and behavioural training, and interactions between all of the above

You played a critical part! And we are extremely grateful

Thank you for your interesting paper too!

I think this is consistent with our findings in mice that hippocampal neuroinflammation enhances goal-directed control. Depression is linked with hippocampal neuroinflammation. Paper if you're interested:

www.sciencedirect.com/science/arti...

I suspect this effect might be different for aged mice

I guess they're better than the ones that charge $10k though.

Best meeting ever!

Congrats Mel xo

Oooh interesting. I'd love to know how you did it.

Just between you and me (and anyone reading this post, lol), we have some more recent data in which we've induced neuroinflammation in NAC core which prevents rats from showing sign-tracking, but they still show a VMAC effect on measures.

Very cool!

Oh sorry!

co-authors that are on bluesky:

@poppywat.bsky.social, @karlyt.bsky.social