Cortical effects of subthalamic stimulation correlate with behavioral recovery from dopamine antagonist induced akinesia.
High-frequency stimulation of around 130 Hz delivered to the subthalamic nucleus (STN-DBS [deep brain stimulation]) is an effective treatment of Parkinson's disease (PD), but the mechanisms of its therapeutic effect remain obscure. Recently, it has been shown in anaesthetized rats that STN-DBS antidromically activates cortical neurons with coincident reduction of the cortical slow wave oscillations that occur in this preparation. Here we extend this work; recording the effect of STN-DBS upon cortical EEG and akinesia, in unanesthetized rats rendered cataleptic by acute dopaminergic blockade. STN-DBS-like stimulation resulted in a short latency, presumed antidromic, evoked potential in the cortex. In cataleptic animals, there was a significant increase in the power of beta oscillations in the electroencephalography which was reversed by stimulation that evoked the cortical response. We also observed a significant rescue of motor function, with the level of akinesia (bar test score) being inversely correlated to the amplitude of the evoked potential (R2 = 0.84). These data confirm that (probably antidromic) short latency cortical responses occur in the awake animal and that these are associated with reductions in abnormal cortical oscillations characteristic of PD and with improvements in akinesia. Our results raise the possibility that STN-DBS reduces PD oscillations and symptoms through antidromic cortical activation.
Dejean
Cyril
C
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
Hyland
Brian
B
Arbuthnott
Gordon
G
D000818:Animals; D001522:Behavior, Animal; D001552:Benzazepines / Q000633:toxicity; D001611:Beta Rhythm; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D046690:Deep Brain Stimulation; D018492:Dopamine Antagonists / Q000633:toxicity; D065127:Dopamine D2 Receptor Antagonists; D005071:Evoked Potentials; D008297:Male; D020891:Raclopride / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D020531:Subthalamic Nucleus / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D020891:Raclopride