Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.
Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. Application of pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Furthermore, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. Thus, closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.
Department of Medical Neurobiology (Physiology), The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical Association School of Medicine and Hadassah University Hospital, Jerusalem 91120, Israel. boris.rosin@mail.huji.ac.il
Boris
B
Rosin
Maya
M
Slovik
Rea
R
Mitelman
Michal
M
Rivlin-Etzion
Suzanne N
SN
Haber
Zvi
Z
Israel
Eilon
E
Vaadia
Hagai
H
Bergman
D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D002522:Chlorocebus aethiops; D046690:Deep Brain Stimulation / Q000379:methods*; D005917:Globus Pallidus / Q000503:physiopathology*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D009474:Neurons / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome