Andrea Luppi, PhD

1/ 🚨 Just out in @natneuro.nature.com! 🧠 We profiled >6,000 features of brain dynamics across humans, macaques, marmosets, mice, fish and worms 🧑🐒🐒🐁🐟🪱 to find a shared neural endpoint of anaesthesia: spatiotemporal isolation of local activity 🧵👇 🔗 doi.org/10.1038/s41593-026-02460-4

10/ Extra special thanks to @bendfulcher.bsky.social for developing HCTSA & to him and NetNeuroLab's @misicbata.bsky.social & @goliashf.bsky.social for inspiring & supporting me to pursue this project over many years 🙏

11/ Want the full story? 📖 Open Access 👉 doi.org/10.1038/s415... Also check out the wonderful commentary in @natneuro.nature.com by George Mashour & Zirui Huang doi.org/10.1038/s415...

8/ Microscale to macroscale mechanism A biophysical model simulating the prolonged inhibitory postsynaptic currents of GABAergic anaesthetics at the microscale, reproduces 461/485 (95%) of macroscale empirical features 🤯 Shortening excitation (à la ketamine) also gets >90% ✅

9/ Team effort across labs & continents 🌍🙏 Thanks to @bechir-jarraya.bsky.social @gozziale.bsky.social @estamatakis.bsky.social @jordytasserie.bsky.social & all great colleagues from NeuroSpin, @riken-sciverse.bsky.social @ulaval.ca @brighamandwomens.bsky.social @tum.de who made this possible!

6/ Spatio-temporal isolation 🌐 Anaesthesia desynchronises regions & decouples their dynamical profiles Neural activity fails to persist over time, but it also fails to propagate in space.

7/ Do conserved dynamics have conserved molecular underpinnings? 🧬 We integrate gene expression from human, macaque & mouse, plus new marmoset genes 🐒🧬 We find a conserved anterior-posterior cortical gradient linking dynamics to genes for excitation & inhibition, including known anesthetic targets

4/ Do any features change in the SAME direction in EVERY contrast & drug & species? 🎯 485 survive (vs ~1 expected by chance!) We consistently find ⬇️ autocorrelation, ⬆️ forecasting error 🔮. Under anaesthesia, information does not persist in neural activity

5/ We measured intrinsic neural timescales directly ⏱️ In every single species, timescales get shorter under anaesthesia, and regions with the longest timescales lose the most ⚖️ DBS of the centromedian thalamus reverses this: timescales lengthen as the macaque wakes up 🐒⚡

2/ Anaesthetics work across species: How? Most studies look at just a few features in 1-2 species 🤔 We used Highly Comparative Time-Series Analysis (HCTSA) to extract >6,000 features of neural activity 📈 from fMRI & calcium imaging in human + macaque + marmoset + mouse + zebrafish + c.elegans

3/ We compare every feature in every region, awake vs anaesthesia Across 7 anaesthetics, 9 orders of magnitude in scale & ~700M years of evolution 🪱🐟🐁🐒🧑, many features shift the same way in every species. And when centromedian thalamic DBS re-awakens the macaque, they flip back⚡

16 Sept

Such an incredible feeling, knowing that the European Research Council believes in our work & and has decided to back my vision for the future of integrative neuroscience 🧠 Grateful beyond words to the collaborators & mentors who made this all possible: here's to doing more science together! 🎉

Department of Psychiatry, University of Oxford@oxfordpsychiatry.bsky.social

👏 Many congratulations to Dr Andrea Luppi, who has been awarded a prestigious European Research Council (ECR) Starting Grant, worth €1.5 million for a period of up to five years. Read more: tinyurl.com/yx85x5kw

dx.doi.orgPhylogeny of Cortical‐Hippocampal Projections Reveals Selective Elimination of Input From Sensory RegionsThe study of cross-species differences in the organization of the cerebral cortex received significant attention during the past century. However, the evolutionary principles governing changes in bra...

11 Sept

Wonderful cross-species work, comparing unimodal-transmodal information across evolution: the field needs more of this, and it's great to see it out!

Daniel Reznik 🎶@reznikdaniel.bsky.social

Now out in Hippocampus!! 📣💥 We examined anatomical inputs to the hippocampal region in six species - the tenrec, rat, marmoset, cat, macaque, and human - and found that hippocampal processing operates on fundamentally different types of information across species! (1/3) dx.doi.org/10.1002/hipo...

rdcu.beUnlocking spontaneous cognition in the age of data scienceNature Reviews Neuroscience - Spontaneous brain activity is experimentally unconstrained. Embracing this freedom unlocks rich opportunities beyond task-based and naturalistic paradigms, the...

1/ What can resting-state neuroimaging offer cognitive and translational neuroscience🧠? Turns out: a lot! 🧵 Long in the making, short in the reading: “Unlocking spontaneous cognition in the age of data science" is out now in @natrevneuro.nature.com rdcu.be/ftWBh

4/ Rest, tasks, movies 🎞️: let us not jostle for who should be center-stage in neuroscience. The stage is large enough for all, and they all have their unique part to play for linking mind and 🧠

doi.orgUnlocking spontaneous cognition in the age of data science - Nature Reviews NeuroscienceSpontaneous brain activity is experimentally unconstrained. Embracing this freedom unlocks rich opportunities beyond task-based and naturalistic paradigms, the traditional Herculean pillars of constra...

5/ Very grateful to my inspiring co-authors from across the spectrum of cognitive, clinical, and translational neuroscience: @helenagellersen.bsky.social @lorinanaci.bsky.social @gozziale.bsky.social @daniel-bor.bsky.social Read the full article here: doi.org/10.1038/s415...

2/ The cognitive value of resting-state neuroimaging is actually *growing* in the age of data science 📈 We are getting better at decoding potential cognitive contents that were already present in spontaneous brain activity—but previously locked away 🔐 and inaccessible.

3/ The unconstrained nature of rest can become a feature, instead of a limitation. We can compare species 🐭🐒, investigate perturbations of consciousness 💊 & understand the extremes of the human lifespan: from in utero 🤰 to advanced dementia and disorders of consciousness 🤕

the-one-percent.qedscience.comQED — The most compelling preprints of 2025

25 June

Our work "Comprehensive profiling of anaesthetised brain dynamics across phylogeny" selected as Top 1% among 57,455 bioRxiv preprints by QED Science 🤩 Check out all top 1%: the-one-percent.qedscience.com Grateful to @misicbata.bsky.social & all co-authors for making this possible! #The1Percent

20 May

Delighted that our paper about benchmarking gene expression 🧬 in macaque brain 🐒🧠(www.science.org/doi/10.1126/...) was selected for this year's Brain Star Award of the Canadian Neuroscience Association 🇨🇦 - what an honour to be named among such talented scientists!

science.orgscience.org

Canadian Association for Neuroscience@canacn.bsky.social

CAN and CIHR-INMHA are very proud to announce the winners of the 2025 Brain Star awards. See all their profiles here: can-acn.org/congratulati...

@helenagellersen.bsky.social

20 May

Incredibly grateful for the mentorship and support of @misicbata.bsky.social, the Banting Fellowship 🇨🇦 that funded me, and to all my collaborators and co-authors for making this possible!

Andrea Luppi, PhD reposted

Helena Gellersen

12 May

How does the brain rapidly distinguish similar memories? We use 7T fMRI to show dynamic shifts between pattern separation and reinstatement signals in hippocampal CA3 and DG with changing task demands: doi.org/10.64898/202...

theconversation.comHow to build a digital ‘twin’ of the human brain – what existing models overlookExisting digital models of the human brain risk missing out on what makes you ‘you’.

24 Apr

Curious about our recent @natneuro.nature.com paper on 🧠 brain modelling (doi.org/10.1038/s415...) but low on time/not your field? We wrote a popular science summary in @uk.theconversation.com, explaining what we found & why you should care. Link: theconversation.com/how-to-build...

doi.orgSystematic evaluation of fMRI data-processing pipelines for consistent functional connectomics - Nature CommunicationsThe effects of different choices on preprocessing pipelines for functional connectomics remain unclear. Here, the authors systematically evaluate a multitude of pipelines on resting-state fMRI, reveal...

22 Apr

Honoured to be speaking at today's Prize-winners' session of the @britishneuro.bsky.social Member's Meeting 🏆 Come hear about Credibility in Neuroscience, and our paper with @helenagellersen.bsky.social 🧠 We compared 768 fMRI brain network pipelines - so you won't have to! doi.org/10.1038/s414...

British Neuroscience Association@britishneuro.bsky.social

The BNA Members’ Meeting programme is now live! Join us online 22–23 April for Rapid-fire talks, research communications, posters and more. Free for BNA members - join instantly from £11/year. Explore the full programme and register via bna.org.uk

nature.comConvergent transcriptomic and connectomic controllers of information integration and its anaesthetic breakdown across mammalian brains - Nature Human BehaviourLuppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

The Mammalian Architecture of Information Integration🧠🧬 For #BrainAwarenessWeek, excited to share our latest work about #Neuroscience of #Consciousness in @nathumbehav.nature.com www.nature.com/articles/s41... 🧵👇

11/ Summing Up We identified evolutionarily conserved principles of mammalian 🧠 architecture Neural information integration is governed by a specific synergy between connectomics and transcriptomics, with PVALB inhibitory gradients and central-thalamic switch acting as key gatekeepers 🤝

12/ Synergistic effort 🙏 Huge thanks to my co-authors @jordytasserie.bsky.social, Lynn Uhrig, & the incredible teams across 3 continents! 🇬🇧🇫🇷🇮🇹🇩🇪🇯🇵🇺🇸🇨🇦 @frosas.bsky.social Pedro Mediano, @parkersingleton.bsky.social, @zhenqi.bsky.social, @bechir-jarraya.bsky.social @gozziale.bsky.social

9/ Inhibition Controls Controllability Species-specific models with heterogeneous inhibition also show that PVALB is anatomically well-suited to tune 🧠 controllability Consciousness may rely on conserved interplay between the brain's wiring diagram and its molecular tuning🧬

10/ Working Model of Thalamic Restoration Species-specific biophysical modelling of macaque 🧠 successfully recapitulates restoration of integration (ΦR) by central but not ventral thalamus DBS: connectivity profile is key! Next: model-based virtual clinical trial in disorder of consciousness?

7/ PVALB Inhibition? We mapped the regional breakdown of ΦR against species-specific gene expression 🧬 in 3 species 👱🐒🐭 Spatial topography of ΦR breakdown coincides with PVALB gene expression (parvalbumin interneurons). This suggests a role for PV-mediated inhibition in governing integration

8/ Biophysical Modelling To go beyond correlation, we built computational models 💻🔬 integrating species-specific anatomical wiring with 🧬 gradients for humans, macaques, & mice Only models with PVALB-driven inhibition successfully recapitulate breakdown of ΦR/integration

5/ Tracking Behaviour Dominance Analysis shows that ΦR outperforms traditional Φ and other proposed information-theoretic measures of "integration" 📊⚖️ for tracking DBS-induced changes in behavioural arousal

6/ Out of Control As the system disintegrates, the brain's dynamics become significantly harder to "control" in a network-theoretic sense 🌀 Loss of controllability scales with breakdown of integration (& is restored by CT-DBS)

3/ Convergent Breakdown The results were striking: across 4 mammalian species 👱🐒🐵🐭 and 6 molecularly diverse drugs, anaesthetic-induced disconnection from environment is marked by a convergent collapse of ΦR 📉 (but *not* traditional Φ or related measures) - rising again upon recovery 📈

4/ Reversing the Collapse via Thalamus⚡️🧠 When macaque🐒 is re-awakened by deep-brain stimulation of central thalamus (CT), we also re-ignite ΦR & the brain’s integrative capacity 🔥 Not so for DBS of a control site! CT is a local switch for the global informational architecture

1/ The Big Picture We combined fMRI, information theory, & species-specific computational modelling in human, macaque, marmoset and mouse 👱🐒🐵🐭 to ask: does anaesthesia reduce the 🧠's capacity to be "more than the sum of its parts"?

2/ From Φ to ΦR 🔥 How do you measure "integration"? Information decomposition reveals that influential measures of "whole-minus-sum-of-parts" double-count the redundancy in the parts. Our revised Φ (ΦR) is a principled solution📊⚖️

nature.comCompetitive interactions shape mammalian brain network dynamics and computation - Nature NeuroscienceBrain network architecture may balance cooperation and competition across circuits. Here the authors use computational whole-brain modeling across three species to show that models with competition ar...

Just out in @natneuro.nature.com! 🧠 “Competitive interactions shape mammalian brain network dynamics and computation” www.nature.com/articles/s41... Is large-scale brain communication purely cooperative — or is competition a core organizing principle? We built 🧠 models to find out: read on🧵👇

10/ Open code! Check out our code for the cooperative-cpmpetitive Hopf model, courtesy of the amazing Hana Ali 👉 github.com/Hana-Ali/com...

11/ Thanks 🙏 Extremely grateful to Hana & also Yoni Sanz Perl, Jakub Vohryzek, @frosas.bsky.social @gozziale.bsky.social, @misicbata.bsky.social, Morten Kringelbach, Gustavo Deco & all other co-authors, for making this team effort possible!

8/ Computational consequences Competitive interactions improve computational capacity, when the model’s generative connectivity is used as the wiring diagram for a connectome-based reservoir network 🤖 Could competition lie behind the efficiency of mammalian👱🐒🐭 brains? 🤔

9/ Outlook 🔭 Competitive interactions are 🗝️ for realistic computational models Macroscale competition may be a conserved principle of mammalian 🧠 organization Implications for more personalised digital twins in medicine ♊️, & designing biologically inspired AI systems

6/ Consistent network topology of competition Competitive connections are not randomly distributed. In each species🐒🐭, negative connections tend to be longer-range than positive ones, and less modular & locally clustered

7/ Not just "more parameters"... Allowing negative connections provides greater performance gains than doubling (!) the number of model parameters. Want more? Check out our Supplementary for extensive validations & more sanity checks

4/ Dynamical consequences It is not just FC that improves, either. After all, that was the model objective. But by allowing competitive interactions, we also get more realistic 🧠 dynamics : synergy, local-global broadcasting, metastability, and irreversibility. For free!

5/ Biological annotations Across species 🐭🐒, competitive interactions are grounded in 🧠 biology They link regions at opposite ends of the cortical hierarchy, with opposite molecular 🧬 and cytoarchitectonic profiles. Competition may help segregate functionally diverse systems

2/ Improved fit Competitive interactions dramatically improve model fit to human, 🐒 & 🐭 FC. The model does not *have to* include negatives – but it chooses to! In humans, competition improves model "cognitive matching" to >100 meta-analytic patterns from NeuroSynth

3/ From distant cousins to digital twins ♊️ Each 🧠 has a unique fingerprint. But traditional cooperative-only models miss its essence: your model and a random stranger's are easily confused. Hardly "personalised"... Allow competition, and it becomes clear which model was yours!