title: Closing the loop of deep brain stimulation.
abstract: High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.
authors.affiliation: Aix Marseille Université UMR 901 Marseille, France ; Institut national de la Recherche Médicale et de la Santé Inserm, INMED UMR 901 Marseille, France ; APHM, Hopital de la Timone, Service de Neurochirurgie Fonctionnelle et Stereotaxique Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Carron
authors.affiliation: Laboratoire des Signaux et Systèmes(L2S), CNRS UMR 8506 Gif-sur-Yvette, France ; Université Paris Sud 11, UMR 8506, Supélec Gif-sur-Yvette, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillet
authors.affiliation: Aix Marseille Université UMR 901 Marseille, France ; Institut national de la Recherche Médicale et de la Santé Inserm, INMED UMR 901 Marseille, France.
authors.forename: Anton
authors.initials: A
authors.lastname: Filipchuk
authors.affiliation: Laboratoire des Signaux et Systèmes(L2S), CNRS UMR 8506 Gif-sur-Yvette, France ; Centre national de la recherche scientifique Paris, France.
authors.forename: William
authors.initials: W
authors.lastname: Pasillas-Lépine
authors.affiliation: Aix Marseille Université UMR 901 Marseille, France ; Institut national de la Recherche Médicale et de la Santé Inserm, INMED UMR 901 Marseille, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Hammond
keywords: DBS; antidromic; closed loop; mechanisms; open loop