Resonance in subthalamo-cortical circuits in Parkinsons disease

Neuronal activity within and across the cortex and basal ganglia is pathologically synchronized, particularly at 20Hz in patients with Parkinsons disease. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes like Parkinsons disease. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus (STN) at various frequencies between 5 and 30Hz in two cohorts of eight patients with Parkinsons disease from two different surgical centres. We found that evoked activity consisted of a series of diminishing waves with a peak latency of 21ms for the first wave in the series. The cortical evoked potentials (cEPs) averaged in each group were well fitted by a damped oscillator function (r0.9, P0.00001). Fits suggested that the natural frequency of the subthalamo-cortical circuit was around 20Hz. When the system was forced at this frequency by stimulation of the STN at 20Hz, the undamped amplitude of the modelled cortical response increased relative to that with 5Hz stimulation in both groups (P0.005), consistent with resonance. Restoration of dopaminergic input by treatment with levodopa increased the damping of oscillatory activity (as measured by the modelled damping factor) in both patient groups (P0.001). The increased damping would tend to limit resonance, as confirmed in simulations. Our results show that the basal gangliacortical network involving the STN has a tendency to resonate at 20Hz in Parkinsonian patients. This resonance phenomenon may underlie the propagation and amplification of activities synchronized around this frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in this basal gangliacortical network.