A gamma band specific role of the subthalamic nucleus in switching during verbal fluency tasks in Parkinson's disease.

OBJECTIVE: Decline in verbal fluency is the most consistent and persistent cognitive impairment documented after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We aimed to identify and characterise verbal fluency related processing within the subthalamic nucleus through analysis of local field potentials.

METHODS: Local field potentials were recorded from deep brain stimulation electrodes implanted in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when patients were on medication. Patients performed phonemic and semantic verbal fluency tasks and a control word repetition task to control for the motor output involved in response generation.

RESULTS: Significant increases in local field potential Power (p ≤ 0.05) were seen across a broad gamma frequency band (30-95 Hz) during both verbal fluency tasks, after controlling for motor output. Increases in gamma local field potential Power of +7.5% ± 2.3% (SEM) in the semantic fluency task and +6.9% ± 2.0% in the phonemic fluency task were derived when averaging across all electrode contact pairs. Gamma changes recorded from contacts lying in the left hemisphere (dominant in verbal fluency) correlated with average number of correct responses generated (r=0.81 p=0.015) and measures of 'switching' (r=0.79 p=0.020) particularly strongly in the semantic fluency task.

INTERPRETATION: Frequency specific power changes observed during task performance are consistent with involvement of the subthalamic nucleus in switching during verbal fluency. Antagonism of such task-related activity with high frequency stimulation of this nucleus may explain the impairments reported.