• Dirk De Ridder, Muhammad Ali Siddiqi, Justin Dauwels, Wouter A Serdijn, and Christos Strydis.
• Section of Neurosurgery, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. Electronic address: dirk.deridder@otago.ac.nz.
• Neuromodulation. 2024 Apr 16.

ObjectivesCurrent techniques in brain stimulation are still largely based on a phrenologic approach that a single brain target can treat a brain disorder. Nevertheless, meta-analyses of brain implants indicate an overall success rate of 50% improvement in 50% of patients, irrespective of the brain-related disorder. Thus, there is still a large margin for improvement. The goal of this manuscript is to 1) develop a general theoretical framework of brain functioning that is amenable to surgical neuromodulation, and 2) describe the engineering requirements of the next generation of implantable brain stimulators that follow from this theoretic model.Materials And MethodsA neuroscience and engineering literature review was performed to develop a universal theoretical model of brain functioning and dysfunctioning amenable to surgical neuromodulation.ResultsEven though a single target can modulate an entire network, research in network science reveals that many brain disorders are the consequence of maladaptive interactions among multiple networks rather than a single network. Consequently, targeting the main connector hubs of those multiple interacting networks involved in a brain disorder is theoretically more beneficial. We, thus, envision next-generation network implants that will rely on distributed, multisite neuromodulation targeting correlated and anticorrelated interacting brain networks, juxtaposing alternative implant configurations, and finally providing solid recommendations for the realization of such implants. In doing so, this study pinpoints the potential shortcomings of other similar efforts in the field, which somehow fall short of the requirements.ConclusionThe concept of network stimulation holds great promise as a universal approach for treating neurologic and psychiatric disorders.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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