Ayda Ghahremani1,2, Adam R Aron3, Kaviraja Udupa2, Utpal Saha2, Duemani Reddy2, William D Hutchison2, Suneil K Kalia2,4, Mojgan Hodaie2,4, Andres M Lozano2,4, Robert Chen2,5,6. 1. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 2. Krembil Research Institute, University Health Network, Toronto, Ontario, Canada. 3. Department of Psychology, University of California, San Diego, La Jolla, CA. 4. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 5. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 6. Edmond J. Safra Program in Parkinson's Disease, University Health Network, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: Many lines of evidence suggest that response conflict recruits brain regions in the cortical-basal ganglia system. Within the basal ganglia, deep brain recordings from the subthalamic nucleus (STN) have shown that conflict triggers a transient increase in low-frequency oscillations (LFOs; 2-8Hz). Here, we deployed a new method of delivering short trains of event-related deep brain stimulation (DBS) to the STN to test the causal role of the STN and its associated circuits in conflict-related processing. METHODS: In a double-blind design, we stimulated the STN in patients with Parkinson disease by locking brief trains of DBS to specific periods of the trial within a Stroop task. RESULTS: Stimulation had a specific effect on conflict compared to nonconflict trials by relatively speeding responses on conflict trials (ie, reducing the Stroop effect, defined as the difference in reaction time between conflict and nonconflict trials) when it was delivered in the preresponse period in the preparation phase. Stimulation also increased errors when it was delivered early in the response window. This latter result corresponded to the timing of the conflict-induced increase in LFOs observed in the absence of stimulation but was not directly related to the reduction in the Stroop effect. INTERPRETATION: These results support the theory that the time of LFO increase recorded from the STN corresponds to a conflict-processing function. They also provide one of the first demonstrations of event-related DBS of the STN in humans during a cognitive control paradigm. Ann Neurol 2018;84:515-526.
OBJECTIVE: Many lines of evidence suggest that response conflict recruits brain regions in the cortical-basal ganglia system. Within the basal ganglia, deep brain recordings from the subthalamic nucleus (STN) have shown that conflict triggers a transient increase in low-frequency oscillations (LFOs; 2-8Hz). Here, we deployed a new method of delivering short trains of event-related deep brain stimulation (DBS) to the STN to test the causal role of the STN and its associated circuits in conflict-related processing. METHODS: In a double-blind design, we stimulated the STN in patients with Parkinson disease by locking brief trains of DBS to specific periods of the trial within a Stroop task. RESULTS: Stimulation had a specific effect on conflict compared to nonconflict trials by relatively speeding responses on conflict trials (ie, reducing the Stroop effect, defined as the difference in reaction time between conflict and nonconflict trials) when it was delivered in the preresponse period in the preparation phase. Stimulation also increased errors when it was delivered early in the response window. This latter result corresponded to the timing of the conflict-induced increase in LFOs observed in the absence of stimulation but was not directly related to the reduction in the Stroop effect. INTERPRETATION: These results support the theory that the time of LFO increase recorded from the STN corresponds to a conflict-processing function. They also provide one of the first demonstrations of event-related DBS of the STN in humans during a cognitive control paradigm. Ann Neurol 2018;84:515-526.
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