iiinova — where your digital self keeps evolving

Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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...

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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 🙏

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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% ✅

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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.

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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 🐒⚡

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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⚡

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 02/10/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 16/09/2026

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! 🎉

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Andrea Luppi, PhD @loopyluppi.bsky.social · 11/09/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 21/07/2026

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 🧠

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Andrea Luppi, PhD @loopyluppi.bsky.social · 21/07/2026

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 🤕

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Andrea Luppi, PhD @loopyluppi.bsky.social · 21/07/2026

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.

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Andrea Luppi, PhD @loopyluppi.bsky.social · 21/07/2026

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

rdcu.be

Unlocking spontaneous cognition in the age of data science

Nature Reviews Neuroscience - Spontaneous brain activity is experimentally unconstrained. Embracing this freedom unlocks rich opportunities beyond task-based and naturalistic paradigms, the...

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Andrea Luppi, PhD @loopyluppi.bsky.social · 25/06/2026

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

the-one-percent.qedscience.com

QED — The most compelling preprints of 2025

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Andrea Luppi, PhD @loopyluppi.bsky.social · 20/05/2026

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!

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Andrea Luppi, PhD @loopyluppi.bsky.social · 20/05/2026

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.org

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Reposted by Andrea Luppi, PhD

Helena Gellersen @helenagellersen.bsky.social · 12/05/2026

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...

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Andrea Luppi, PhD @loopyluppi.bsky.social · 24/04/2026

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...

theconversation.com

How to build a digital ‘twin’ of the human brain – what existing models overlook

Existing digital models of the human brain risk missing out on what makes you ‘you’.

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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 🤝

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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?

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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🧬

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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)

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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 📈

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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📊⚖️

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Andrea Luppi, PhD @loopyluppi.bsky.social · 19/03/2026

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"?

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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!

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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? 🤔

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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!

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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!

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

1/ Introducing competition Most whole-brain models assume that regions cooperate (as A goes up, so does B) Our generative model also allows competitive (negative-sign) interactions. As A gets more active, it can suppress B We test if this improves model fit in human, 🐒 & 🐭

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Andrea Luppi, PhD @loopyluppi.bsky.social · 13/03/2026

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🧵👇

nature.com

Competitive interactions shape mammalian brain network dynamics and computation - Nature Neuroscience

Brain 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...

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Andrea Luppi, PhD @loopyluppi.bsky.social · 08/12/2025

9/ Wonderful collaboration with extremely talented colleagues: Hana Ali, @zhenqi.bsky.social , Filip Milisav, @gozziale.bsky.social , Danilo Bzdok, & @misicbata.bsky.social (& thanks to our AI neuroscience experts 🤖 of course!)

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