Where are the higher-order cognitive functions? The paradox of nonlocality in awake cognitive mapping from a complex dynamic system framework

Jesús Martín-Fernández ^1,2,3* Nayra Caballero-Estebaranz ^2,3 Esteban Félez ^2,4 Natalia Navarro Peris ^1,2 Pedro Pérez del Rosario ^1,2 Raúl Hernández Bisshopp ¹ Jaime Domínguez-Báez ¹

• ¹ University Hospital of the Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
• ² e-Awake Institute, San Cristóbal de La Laguna, Spain
• ³ Canarian Association of Creative Therapies (ASCATEC), Santa Cruz de Tenerife, Spain
• ⁴ ETH Zürich, Zurich, Zürich, Switzerland

This study addresses the challenge of identifying and preserving higher-order cognitivefunctions during neurosurgery from a complex dynamic systems framework.Traditionally, neurosurgical practice has prioritized avoiding language and motor deficits,while higher-order functions—such as social cognition and executive processes—remainunderexplored. These functions arise from dynamic large-scale networks operating in anoptimal balance between synchronization and metastability, rather than from isolated andlocalized cortical regions. Such complexity reveals a paradox of non-locality in awakecognitive mapping: no single area “contains” a function, yet certain “critical points” cantransiently disrupt network dynamics when stimulated intraoperatively. Direct electricalstimulation (provides unique real-time insights by inducing brief dyssynchronizationsthat elicit observable behavioral changes, allowing neurosurgeons andneuropsychologists to pinpoint crucial cortical and subcortical “connectome-stop points”and minimize damage. Preserving deep white-matter tracts is essential, given their limitedneuroplasticity and the profound, often irreversible impact of tract lesions on cognition.To address these challenges, we propose a three-step awake cognitive mapping approach:(1) localizing critical points of networks via DES-driven behavioral impairment, (2)constante monitoring of multiple cognitive domains as tumor resection progresses, and(3) halting resection at connectome-stop points to prevent irreversible deficits. Anillustrative case of a right parietal glioma demonstrates how this methodology integratescomputational neuroscience, network theory, and clinical practice, enabling optimalonco-functional balance and maintaining the patient’s quality of life.