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ERA-NET NEUROFLEX

The Flexible Mind: Brain Network and Cognitive Flexibility as Targets to Treat Chronic Pain

Funded under ERA-NET NEURON Joint Transnational Call 2025 (Interdisciplinary Approaches to the Neuroscience of Pain).

Idea

Chronic pain is highly heterogeneous and often persists without ongoing nociceptive drive, frequently with mood and anxiety comorbidity. NEUROFLEX asks how cognitive flexibility — the capacity to adapt responses to changing demands — mediates and predicts the link between large-scale brain dynamics and pain / mental-health phenotypes.

Across three centrally driven chronic pain conditions (chronic low back pain, fibromyalgia, phantom limb pain), and an experimental expectation-modulation arm, we reconstruct the brain’s large-scale attractor landscape from resting-state fMRI and use mediation-based machine learning to separate direct effects of brain dynamics from effects routed through cognitive flexibility. Models are developed within cohorts and validated across datasets to seek both condition-specific and generalizable neuromarkers.

Programme & sites

ProgrammeERA-NET NEURON JTC 2025
CentresUniversity Medicine Essen (Germany); Sheba Medical Center, Ramat-Gan (Israel); University of Szeged (Hungary)
ConditionsChronic low back pain, fibromyalgia, phantom limb pain; experimentally induced pain under placebo/nocebo expectation modulation
ScaleFive coordinated studies; expected total ~968 participants
MethodsResting-state fMRI attractor landscapes (dwell times, transition structure); cognitive flexibility phenotyping; mediation-based predictive modelling; cross-site harmonisation and external validation

Our lab leads the computational core: free-energy-minimizing attractor network models of large-scale dynamics, predictive modelling across cohorts, pipeline harmonisation, and open tooling (including connattractor / attractome).

Consortium

RolePeople / group
CoordinatorAbigail Livny-Ezer (C.BIRD / Sheba Medical Center, Israel)
Computational neuroimagingTamas Spisak (Predictive Neuroscience Lab, Essen)
Clinical pain neuroscienceUlrike Bingel (Clinical Neuroscience Lab, Essen)
Clinical neuroimagingZsigmond Tamás Kincses, Daniel Vereb (University of Szeged)
Cross-site doctoral linkJenya Lerer

Expected impact

Multidimensional neuromarkers for individual prediction of pain and mental-health symptoms, and modifiable targets (cognitive flexibility; network dynamics) for treatment personalization.