Whole-brain receptor markers and hub excitabilities determine acute and long-term outcomes in stroke
- 1Universitat Pompeu Fabra
Abstract
Following a stroke, changes in receptor systems have been observed that may influence the excitability of affected brain regions and drive recovery trajectories. Translating results from animal studies to patients remains a major challenge, and while imaging modalities have provided a wealth of findings, a mechanistic link between local receptor systems and observed imaging data is still missing. To bridge this gap, we built patient-specific digital twins with their own neuromodulatory profiles: we integrated 19 receptor and transporter density maps into a mechanistic whole-brain model, and estimated their influence on cortical excitability for each stroke patient and how these systems subsequently explain recovery trajectories. We found that distinct receptor profiles modulated excitability in perilesional versus non-perilesional tissue. Favourable acute motor outcomes were most strongly explained by increased inhibition mediated by non-perilesional GABA-A receptors, together with enhanced excitability driven by cannabinoid, histaminergic, and noradrenergic systems. For acute language outcomes, we identified receptor signatures that, together with motor findings, formed two cross-domain clusters linking excitability to either better or poorer performance. Remarkably, structurally highly connected hubs played a key role: their acute excitability explained cognitive and language deficits and predicted language recovery at one year. Together, our results establish a mechanistic link between receptor-specific modulation of cortical excitability and behavioural recovery, highlighting potential targets for pharmacological and non-invasive therapeutic interventions.
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BibTeX
@misc{schulte2026wholebrain,
title = {{Whole-brain receptor markers and hub excitabilities determine acute and long-term outcomes in stroke}},
author = {J. D. Schulte and J. Vohryzek and M. Monge-Asensio and G. Zamora-Lopez and G. A. Patow and Y. Sanz Perl and M. Corbetta and G. Deco},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.755271},
url = {https://www.biorxiv.org/content/10.64898/2026.10.04.755271v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Whole-brain receptor markers and hub excitabilities determine acute and long-term outcomes in stroke
AU - J. D. Schulte
AU - J. Vohryzek
AU - M. Monge-Asensio
AU - G. Zamora-Lopez
AU - G. A. Patow
AU - Y. Sanz Perl
AU - M. Corbetta
AU - G. Deco
PY - 2026
DA - 2026/10/04
PB - bioRxiv
DO - 10.64898/2026.10.04.755271
UR - https://www.biorxiv.org/content/10.64898/2026.10.04.755271v1
AB - Following a stroke, changes in receptor systems have been observed that may influence the excitability of affected brain regions and drive recovery trajectories. Translating results from animal studies to patients remains a major challenge, and while imaging modalities have provided a wealth of findings, a mechanistic link between local receptor systems and observed imaging data is still missing. To bridge this gap, we built patient-specific digital twins with their own neuromodulatory profiles: we integrated 19 receptor and transporter density maps into a mechanistic whole-brain model, and estimated their influence on cortical excitability for each stroke patient and how these systems subsequently explain recovery trajectories. We found that distinct receptor profiles modulated excitability in perilesional versus non-perilesional tissue. Favourable acute motor outcomes were most strongly explained by increased inhibition mediated by non-perilesional GABA-A receptors, together with enhanced excitability driven by cannabinoid, histaminergic, and noradrenergic systems. For acute language outcomes, we identified receptor signatures that, together with motor findings, formed two cross-domain clusters linking excitability to either better or poorer performance. Remarkably, structurally highly connected hubs played a key role: their acute excitability explained cognitive and language deficits and predicted language recovery at one year. Together, our results establish a mechanistic link between receptor-specific modulation of cortical excitability and behavioural recovery, highlighting potential targets for pharmacological and non-invasive therapeutic interventions.
ER -