Congratulations to Gitte Moos Knudsen for being partner in the recently funded EU Horizon-RIA proposal "SYnergistic Neuroplasticity Enhancement via inteGrated neuRomodulation and Individualized Algorithms in MDD (SYNERGIA)". The 5-year project project has received ~8 million EUR in funding under the EU grant activity called HORIZON-HLTH-2025-03-DISEASE-02, and it will be coordinated by Francesca Castaldo from the Barcelona-based company Neuroelectrics. The NRU share of the grant amounts to 1.545.245 Euro.
The SYNERGIA project proposes a paradigm-shifting approach to the treatment of Major Depressive Disorder (MDD) by combining psilocybin-induced neuroplasticity with transcranial direct current stimulation (tDCS)-mediated consolidation, guided by computational whole-brain models. A small abstract for the project can be found below.
Abstract: Major depressive disorder is common, heterogeneous, and too often refractory to standard care. Psilocybin transiently enhances neuroplasticity, with replicated phase II antidepressant efficacy; transcranial direct current stimulation (tDCS) safely modulates cortical excitability, with modest but significant pooled effects, and has recently received FDA clearance for home use. With growing evidence that both work, the critical open question is durability. Synergia tests a personalized therapy that opens a plasticity window with one supervised psilocybin session, then consolidates circuit reconfiguration via multichannel tDCS at home. A multicenter, sham-controlled, two-arm study (refined from the Stage 1 factorial design to maximize power for the maintenance hypothesis; all patients receive open-label psilocybin 25 mg; randomized to active vs. sham tDCS; N=120) will deliver remotely supervised tDCS over eight weeks and follow patients for six months. Harmonized clinical, safety, and mechanistic endpoints (EEG, fMRI) will validate model predictions, enable biotype-based stratification, and identify surrogate markers. In parallel, a mechanistic study in healthy volunteers maps plasticity-enhancement and drug–stimulation synergy via multimodal readouts (TMS-MEP/TEP, EEG, MRI, MRS), providing translational assays and candidate surrogate endpoints. Patient-specific digital twins - computational models of each patient’s brain, calibrated with neuroimaging - will inform response analysis and tDCS personalization. Outputs include a FAIR data resource, sex- and gender-aware biomarkers, and clinical-grade AI-powered digital twin software. Building on the consortium’s track record in home-tDCS trials, psychedelic neuroimaging, and whole-brain modeling, Synergia aims to replace trial-and-error with model-guided
care, increasing remission durability for patients, clinicians, and healthcare systems. The platform offers a scalable blueprint for precision neurotherapeutics.