Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease

• Published in: Movement disorders Vol. 27; no. 7; pp. 864 - 873
• Main Authors: Walker, Harrison C., Huang, He, Gonzalez, Christopher L., Bryant, James E., Killen, Jeffrey, Cutter, Gary R., Knowlton, Robert C., Montgomery, Erwin B., Guthrie, Bart L., Watts, Ray L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2012; Wiley
• Subjects: Aged; Analysis of Variance; Biological and medical sciences; Cerebral Cortex - physiopathology; deep brain stimulation; Deep Brain Stimulation - methods; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electroencephalography; event related potential; Evoked Potentials - physiology; Female; Humans; Male; Medical sciences; Middle Aged; Motor Activity - physiology; Neurology; Nonlinear Dynamics; Parkinson Disease - pathology; Parkinson Disease - therapy; Parkinson's disease; Reaction Time - physiology; Regression Analysis; subthalamic nucleus; Subthalamus - physiology; Nervous system diseases; Parkinson's disease; Deep brain stimulation; Central nervous system; Electrophysiology; Parkinson disease; Electroencephalography; Encephalon; Cerebral disorder; event related potential; Central nervous system disease; Degenerative disease; Subthalamic nucleus; Event evoked potential; Extrapyramidal syndrome
• DOI: 10.1002/mds.25025
• ISSN: 0885-3185

Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the motor symptoms of advanced Parkinson's disease (PD), and additional evidence suggests that it improves refractory symptoms of essential tremor, primary generalized dystonia, and obsessive‐compulsive disorder. Despite this, its therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation activates the cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for PD. In 5 subjects (six hemispheres), EEG measured the response of cortex to subthalamic stimulation across a range of stimulation voltages and frequencies. Novel analytical techniques reversed the anode and cathode electrode contacts and summed the resulting pair of event‐related potentials to suppress the stimulation artifact. We found that subthalamic brain stimulation at 20 Hz activates the somatosensory cortex at discrete latencies (mean latencies: 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 ms, denoted as R1, R2, and R3, respectively). The amplitude of the short latency peak (R1) during clinically effective high‐frequency stimulation is nonlinearly dependent on stimulation voltage (P < 0.001; repeated‐measures analysis of variance), and its latency is less variable than that of R3 (1.02 versus 19.46 ms; P < 0.001, Levene's test). We conclude that clinically effective subthalamic brain stimulation in humans with PD activates the cerebral cortex at 1 ms after stimulus onset, most likely by antidromic activation. These findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region may be an important component of the therapeutic mechanism of subthalamic brain stimulation. © 2012 Movement Disorder Society