From non-human to human primates: the translational approach allowing to enhance resection, safety and indications in gliomas surgery preserving sensorimotor abilities

MATTEO GAMBARETTI ^1,2* Luca Viganò ^2,3 Matteo Gallo ¹ Giovanni Pratelli ¹ Tommaso Sciortino ¹ Lorenzo Gay ¹ Marco Conti Nibali ¹ Alberto Luigi Gallotti ^1,4 Leonardo Tariciotti ¹ Luca Mattioli ¹ Lorenzo Bello ^1,4 Gabriella Cerri ^2,3 Marco Rossi ^1,2*

• ¹ Neurosurgical Oncology Unit, IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy
• ² MoCA Laboratory, Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy
• ³ IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Lombardy, Italy
• ⁴ Department of Oncology and Hematology Oncology, Faculty of Medicine and Surgery, University of Milan, Milan, Lombardy, Italy

Since the pivotal studies of neurophysiologists in the early 20 th century, exploring brain functions in non-human primates contributed to shed light on neural mechanisms subserving neurological function.By using data acquired on non-human primates as a reference, important progress in knowledge of the human brain and its functions has been achieved. The translational impact allowed by this scientific effort must be recognized in the implementation of the current surgical techniques particularly in support of the neurosurgical approach to brain tumors. In the surgical treatment of brain tumors, the ability to maximally extend the resection allows an improvement in overall survival, progression-free survival and quality of life of patients.The main goal and, at the same time, the main challenge, of oncological neurological surgery is to avoid permanent neurological deficit while reaching maximal resection, particularly when the tumor infiltrates the neural network subserving motor functions. Brain mapping techniques were developed to identify with neurophysiological probes, the areas and tracts subserving sensorimotor function to be preserved by the resection. During the last 20 years, starting from the classical "Penfield" technique, brain mapping has been progressively implemented. Among the major advancements was the introduction of the high frequency direct electrical stimulation. Its refinement, along with the complementary use with low frequency stimulation, allowed a further refinement of stimulation protocols.In this narrative review we propose an analysis of the process through which the knowledge acquired through experiments on non-human primates influenced and changed the current approach in neurosurgical procedures. Then, we describe the main available techniques for brain mapping applied to the resection of tumors harboring within sensorimotor circuits. We also detail how these techniques allowed the acquisition of new data on the properties of areas and tracts underlying sensorimotor control, in turn fostering the design of new tools to navigate within cortical and subcortical areas, that were before deemed to be "sacred and untouchable".