Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism

• Published in: Neuron (Cambridge, Mass.) Vol. 72; no. 2; pp. 370 - 384
• Main Authors: Rosin, Boris, Slovik, Maya, Mitelman, Rea, Rivlin-Etzion, Michal, Haber, Suzanne N., Israel, Zvi, Vaadia, Eilon, Bergman, Hagai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.10.2011; Elsevier Limited
• Subjects: Animals; Basal Ganglia - physiopathology; Cercopithecus aethiops; Deep Brain Stimulation - methods; Electrodes; Globus Pallidus - physiopathology; Monkeys & apes; MPTP Poisoning - chemically induced; MPTP Poisoning - physiopathology; MPTP Poisoning - therapy; Neurons - physiology; Neurosciences; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - physiopathology; Parkinson Disease, Secondary - therapy; Parkinson's disease; Primates; Treatment Outcome
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2011.08.023

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. ► Novel DBS based on neuronal activity (closed-loop, CL-DBS) is superior to standard DBS ► Corticopallidal CL-DBS yields greater alleviation of parkinsonian akinesia ► Corticopallidal CL-DBS yields greater reduction of oscillatory neuronal discharge ► Pallidopallidal CL-DBS leads to dissociation between discharge rate and patterns