32. Resonance in subthalamo-cortical circuits in Parkinson’s disease

Alexandre Eusebio1 a.eusebio@ion.ucl.ac.uk Alek Pogosyan1 a.pogosyan@ ion.ucl.ac.uk Shouyan Wang2 sy.wang@soton.ac.uk Bruno Averbeck1 b.averbeck@ion.ucl.ac.uk Louise Doyle Gaynor1 l.doyle@ion.ucl.ac.uk Patricia Limousin1,3 p.limousin@ion.ucl.ac.uk Peter Brown1 p.brown@ion.ucl.ac.uk

1Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology - UCL, London, UK
2Hearing and Balance Centre, Institute of Sound and Vibration Research, University of Southampton, Southampton, UK
3Unit of Functional Neurosurgery, Institute of Neurology - UCL, London, UK

Neuronal activity within and across the cortex and basal ganglia often synchronizes at ~20 Hz in patients with Parkinson’s disease and is linked to impaired movement. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus, a key basal ganglia structure, in parkinsonian patients. We stimulated at various frequencies between 5 and 30 Hz. By fitting a damped oscillator function to the cortical response obtained during 5 Hz stimulation in patients off dopaminergic therapy we found that the natural frequency of the subthalamo-cortical circuit is around 20 Hz. When the system was forced at this frequency by stimulation of the subthalamic nucleus at 20 Hz, the undamped amplitude of the cortical response increased (3.1 0.7 μV and 1.8 0.1 μV with stimulation at 20 Hz and 5 Hz, p = 0.0053) due to resonance phenomena. Restoration of dopaminergic input by treatment with the dopamine prodrug, levodopa, increased the damping factor of oscillations by 30 % (0.18 0.01 and 0.14 0.01 on and off levodopa, p = 0.001), thereby limiting resonance phenomena. Our results show that the basal ganglia – cortical network has a tendency to resonate at ~20 Hz in parkinsonian patients. This resonance phenomenon underlies the propagation and amplification of activities synchronized around this critical frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in the basal ganglia – cortical network.