Deep brain stimulation: eye movements reveal anomalous effects of electrode placement and stimulation

One of the major difficulties in evaluating the efficacy of deep brain stimulation (DBS), or understanding its mechanism, is the need to distinguish the effects of stimulation itself from those of the lesion inevitably created during surgery. Recent work has shown that DBS of the subthalamic nucleus in Parkinson's disease greatly reduces the time it takes the eyes to make a saccade in response to a visual stimulus. Since this saccadic latency can be rapidly and objectively measured, we used it to compare the effects of surgery and of stimulation. We used a saccadometer to measure the saccadic latencies of 9 DBS patients (1) preoperatively, (2) the day after insertion of subthalamic nucleus electrodes, (3) three weeks later, prior to turning on the stimulator, and (4) after commencement of stimulation. Patients were on their anti-Parkinsonian medication throughout the study. It revealed an entirely unexpected and puzzling finding. As in previous studies an amelioration of symptoms is seen immediately after surgery, and then a further improvement when finally the stimulator is turned on, but in the case of saccadic latency the pattern is different: surgery produces a transient increase in latency, returning to baseline within three weeks, while subsequent stimulation reduced latency. Thus the differential effects of electrode placement and stimulation are completely different for saccades and for more general motor symptoms. This important finding rules out some over-simple interpretations of the mechanism of DBS, and needs to be taken into account in future attempts at modelling the neurophysiology of DBS.