Introduction: In Parkinson’s patients in the OFF medication state, basal ganglia local field potentials exhibit characteristic changes in beta and gamma oscillations that may be directly related to the symptoms of rigidity and bradykinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG) studies of sensorimotor cortex suggest that changes in cortical oscillations in Parkinson’s patients may differ from those of the basal ganglia during the OFF medication state.

Methods: To further explore sensorimotor cortex oscillatory activity in Parkinson’s disease (PD), we performed high-resolution ECoG (2-6 contacts per gyrus and 1-2 contacts per sulcus) recordings intra-operatively in patients undergoing deep brain stimulator placement in the awake state. We analyzed ECoG potentials during a computer-controlled task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in patients with essential tremor (ET), a condition not associated with rigidity or bradykinesia.

Results: We show that 1) cortical beta spectral power is not different between PD and ET patients, 2) motor preparation in Parkinson’s patients in the OFF medication state is associated with increased cortical beta reactivity compared to patients with ET, and 3) cortical broadband gamma power is elevated compared to ET patients during both rest and task recordings.

Conclusions: Our findings are suggestive of an inverse oscillatory profile in sensorimotor cortex of Parkinson’s patients that, in contrast to basal ganglia, may act to facilitate movement in the face of an antikinetic bias inherent in the dopamine-depleted state.

Patient Care: Understanding oscillatory patterns in diseases of the brain is critical to identifying novel neuromodulation-based therapies for patients affected with these disorders. As an example, a closed-loop device for treating refractory seizures is based on sensing abnormal oscillations from chronically implanted electrodes in epilepsy patients. Studies are underway to create similar devices in patients with movement disorders, however the oscillatory patterns in those diseases are not fully understood. The research described herein is thus central to that effort and may hopefully lead to improved symptom control in patients suffering from neurodegenerative disorders.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of spectral changes in local field potential recordings in patients with Parkinson's disease, 2) Discuss, in small groups, the differences between spectral changes in basal ganglia and cortex in local field potential recordings in patients with Parkinson's disease, and 3) Identify an effective treatment using neuromodulation based on the spectral changes discussed in 1 and 2 above.

References: 1. Oswal, A., Litvak, V., Sauleau, P. & Brown, P. Beta reactivity, prospective facilitation of executive processing, and its dependence on dopaminergic therapy in Parkinson’s disease. J. Neurosci. 32, 9909–9916 (2012). 2. Joundi, R. A. et al. Oscillatory activity in the subthalamic nucleus during arm reaching in Parkinson’s disease. Exp. Neurol. 236, 319–326 (2012). 3. Brown, P. et al. Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J. Neurosci. 21, 1033–1038 (2001). 4. Androulidakis, A. G. et al. Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson’s disease. Brain 130, 457–468 (2007). 5. Engel, A. K. & Fries, P. Beta-band oscillations—signalling the status quo? Curr. Opin. Neurobiol. 20, 156–165 (2010). 6. Jenkinson, N., Kühn, A. A. & Brown, P. ? oscillations in the human basal ganglia. Exp. Neurol. 245, 72–76 (2013). 7. Crowell, A. L. et al. Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study. Brain 135, 615–630 (2012). 8. Koop, M. M., Andrzejewski, A., Hill, B. C., Heit, G. & Bronte-Stewart, H. M. Improvement in a quantitative measure of bradykinesia after microelectrode recording in patients with Parkinson’s disease during deep brain stimulation surgery. Mov. Disord. 21, 673–678 (2006). 9. Brown, P. et al. Dopamine Dependency of Oscillations between Subthalamic Nucleus and Pallidum in Parkinson ’ s Disease. 21, 1033–1038 (2001). 10. Little, S., Pogosyan, A., Kuhn, A. A. & Brown, P. ß band stability over time correlates with Parkinsonian rigidity and bradykinesia. Exp. Neurol. 236, 383–388 (2012). 11. Welch, P. D. The use of fast Fourier transform for the estimation of power spectra: A method based on time averaging over short, modified periodograms. IEEE Trans. Audio Electroacoust. 15, 70–73 (1967). 12. Allen, J. Short term spectral analysis, synthesis, and modification by discrete Fourier transform. IEEE Trans. Acoust. 25, 235–238 (1977). 13. Yousry, T. A. et al. Localization of the motor hand area to a knob on the precentral gyrus. A new landmark. Brain 120 ( Pt 1, 141–157 (1997). 14. Arnold, T. B. & Emerson, J. W. Nonparametric goodness-of-fit tests for discrete null distributions. R J. 3, 34–39 (2011). 15. Storey, J. D. A direct approach to false discovery rates. J. R. Stat. Soc. Series B Stat. Methodol. 64, 479–498 (2002). 16. Crone, N. E. et al. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. I. Alpha and beta event-related desynchronization. Brain 121 ( Pt 1, 2271–2299 (1998). 17. Kühn, A. A. et al. Modulation of beta oscillations in the subthalamic area during motor imagery in Parkinson’s disease. Brain 129, 695–706 (2006). 18. Miller, K. J. et al. Spectral changes in cortical surface potentials during motor movement. J. Neurosci. 27, 2424–2432 (2007). 19. De Lange, F. P., Jensen, O., Bauer, M. & Toni, I. Interactions between posterior gamma and frontal alpha/beta oscillations during imagined actions. Front. Hum. Neurosci. 2, 7 (2008). 20. Marceglia, S. et al. Modulation of beta oscillations in the subthalamic area during action observation in Parkinson’s disease. Neuroscience 161, 1027–1036 (2009). 21. Jenkinson, N. & Brown, P. New insights into the relationship between dopamine, beta oscillations and motor function. Trends Neurosci. 34, 611–618 (2011). 22. Kühn, A. a et al. High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson’s disease in parallel with improvement in motor performance. J. Neurosci. 28, 6165–6173 (2008). 23. Hammond, C., Bergman, H. & Brown, P. Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci. 30, 357–364 (2007). 24. Little, S. & Brown, P. The functional role of beta oscillations in Parkinson’s disease. Parkinsonism Relat. Disord. 20 Suppl 1, S44–8 (2014). 25. Sharott, A. et al. Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat. Eur. J. Neurosci. 21, 1413–1422 (2005). 26. Lalo, E. et al. Patterns of bidirectional communication between cortex and basal ganglia during movement in patients with Parkinson disease. J. Neurosci. 28, 3008–3016 (2008). 27. Shimamoto, S. a et al. Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson’s disease. J. Neurosci. 33, 7220–7233 (2013). 28. Moran, A., Bergman, H., Israel, Z. & Bar-Gad, I. Subthalamic nucleus functional organization revealed by parkinsonian neuronal oscillations and synchrony. Brain 131, 3395–3409 (2008). 29. Rosin, B. et al. Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron 72, 370–384 (2011). 30. De Hemptinne, C. et al. Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc. Natl. Acad. Sci. U. S. A. 110, 4780–4785 (2013). 31. Miller, K. J. et al. Human Motor Cortical Activity Is Selectively Phase- Entrained on Underlying Rhythms. PLoS Comput. Biol. 8, e1002655 (2012). 32. Yanagisawa, T. et al. Regulation of motor representation by phase-amplitude coupling in the sensorimotor cortex. J. Neurosci. 32, 15467–15475 (2012). 33. Shibasaki, H. Human brain mapping: hemodynamic response and electrophysiology. Clin. Neurophysiol. 119, 731–743 (2008). 34. Huang, C. et al. Changes in network activity with the progression of Parkinson’s disease. Brain 130, 1834–1846 (2007). 35. Ko, J. H. et al. Parkinson’s disease: increased motor network activity in the absence of movement. J. Neurosci. 33, 4540–4549 (2013). 36. Joundi, R. A., Jenkinson, N., Brittain, J.-S., Aziz, T. Z. & Brown, P. Driving oscillatory activity in the human cortex enhances motor performance. Curr. Biol. 22, 403–407 (2012).