shockingly objective take 😉

Congrats, amazing! Well deserved, and no surprise :-)

Interesting proposal. How about editors using LLMs not to generate reviews, but to flag those that look generic and light on insight? And also use LLMs to cross-check reviews for factual errors, since some reviews can be confidently wrong.

We'll miss you here Ilya! Exciting opportunity, congrats! Wishing you all the best for this next chapter!

💔 that’s really tough, so sorry

Thanks CJ!

14/ Finally, this work wouldn’t have been possible without generous support from many funders. Special thanks to the NIH, especially NIMH, NIDA, and the NIH Pioneer Award—for making long-term, high-risk neuroscience like this possible.
🧵🔚

13/ This builds on decades of work linking inflammation to fatigue, depression, and motivation loss. We’re picking up that thread, now with a defined brain circuit in play, a step toward circuit neuro-immunology.
#Inflammation #Depression #IL6 #Cancer #Cachexia #NeuroImmunology

12/ This project took a *huge* team, spanning neuroscience, immunology, and cancer. Grateful to co–first authors Aelita Zhu, Sarah Starosta, co–senior authors Marco Pignatelli & Tobias Janowitz & ours labs & all our amazing collaborators including @kravitzlab.com & Pavel Osten.

11/ We’re also excited about our effort-based tasks to measure motivation. Grounded in behavioral economics, they’re designed for cross-species computational psychiatry. We’re now adapting them for humans to bridge physical disease and psychiatric symptoms.

10/ Our work reframes cachexia: it’s not just body wasting, it inherently involves the brain. Chronic inflammation activates a neural circuit that suppresses motivation—likely
adaptive in acute illness but harmful when chronic, showing how physical disease directly causes psychiatric symptoms.

9/ We also used an IL-6–blocking antibody in mice—similar to FDA-approved drugs for rheumatoid arthritis. Given early, it improved survival. Given late, it still rescued apathy-like behavior. This points to a promising, translatable way to treat apathy in advanced disease.

8/ The circuit insights let us reverse apathy without stopping cancer:
— Knockdown of IL-6 receptors in area postrema
— Ablation of ArP→PBN neurons
— Boosting dopamine via optogenetics or dopamine agonist cocktail injected in nucleus accumbens.
Motivation was rescued even in late-stage disease.

7/ We used a patch foraging task with depleting rewards designed to measure effort sensitivity—grounded in behavioral economics. As cachexia progressed and IL-6 rose, dopamine in the nucleus accumbens fell. Mice gave up faster, even when rewards were still available.

6/ We mapped fill the circuit: IL-6 activates the area postrema neurons that project parabrachial nucleus and then to substanta nigra pr, which inhibits dopamine release in the nucleus accumbens. Optogenetic activation of ArP→PBN mimicked inflammation, rapidly suppressing motivation.

5/ To find the cause, we ran a cytokine screen and brainwide cFos mapping. The cytokine IL6 increased with cachexia. Most brain regions were suppressed, but a few lit up—most notably the area postrema, a circumventricular organ outside the BBB that could sense circulating IL-6.

4/ We tested in mice with cancer (C26 colon adenocarcinoma) and saw a striking loss of motivation.
As cachexia set in, effort sensitivity increased in two tasks—but mice still liked sweet rewards, showed no despair, and retained capacity to move. Apathy-like behavior.

3/ Apathy in cancer cachexia is often dismissed as a psychological reaction to physical decline. But what if it’s part of the disease process itself—driven by inflammation acting on the brain?

2/ Cachexia affects ~80% of late-stage cancer patients. It’s a wasting syndrome with severe weight/muscle loss despite eating. But it also drains the mind—patients lose motivation, withdraw from loved ones, and struggle with treatment. Apathy and fatigue take over.