Neuronal oscillations, rhythmic changes in neuronal excitability that result from the activity of synchronized groups of neurons, are now commonly recorded through a variety of techniques. The result has been an increased focus on elucidating their potential role in the regulation of local stimulus processing and long-range information transfer in the human brain. Traditional modal frequency bands, delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz) and gamma (>30 Hz), that separate oscillatory activity with distinct spatial and temporal scales have been found to be integrated by a phenomenon called phase-amplitude cross-frequency coupling. Phase-amplitude coupling typically describes the statistical dependence between the phase of a low-frequency brain rhythm and the amplitude (or power) of the high-frequency component of electrical brain activity. The exact frequencies that couple have been found to vary as a function of the brain areas and tasks studied.1
Aberrant cross-frequency coupling may play a role in functional brain disorders. De Hemptinne et al specifically investigated whether the pathological β-band neuronal synchronization previously described in the basal ganglia of Parkinson disease (PD) patients is associated with abnormal coupling of oscillatory activity in the motor cortex (Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci. 2013;110(12):4780-4785.).2 The authors investigated this question by sliding a strip electrode through the burr hole during deep brain stimulator implantation and simultaneously recording local field potentials from the primary motor cortex and subthalamic nucleus (STN). In comparison to patients with primary craniocervical dystonia undergoing STN deep brain stimulation (DBS) and epilepsy patients undergoing ECoG, PD patients exhibited abnormal coupling within the primary arm motor cortex (M1) and between the subthalamic nucleus and M1. In M1, the magnitude of β-phase to broadband-γ amplitude coupling was much greater in PD patients. In addition, significant coupling between STN β-phase and M1 γ-amplitude was stronger and more frequent in PD patients, with the strongest cortical modulation preceded the STN β-trough, suggesting that cortical LFP changes precede those in STN. Furthermore, the investigators were able to study the effects of therapeutic DBS parameters in 2 of 15 patients, and remarkably, the exaggerated cortical phase-amplitude coupling was reversibly suppressed by STN stimulation.
De Hemptinne et al propose that akinesia in PD may result from excessive M1 phase-amplitude coupling that renders the cortex less able to respond dynamically to signals from other cortical regions, such as frontal executive areas involved in internally directed movement. Based on the STN stimulation effects, they also suggest that the magnitude of cortical phase-amplitude coupling may be useful in the future as a control signal for closed-loop therapeutic deep brain stimulation involving chronically implanted cortical electrodes. Lastly, the authors point out that their data indicating STN β-troughs are preceded by β-modulated waves of cortical broadband-γ is consistent with a potential mechanism for cortical feedback in maintaining pathological basal ganglia oscillations. In addition to identifying a novel, potential electrophysiological biomarker of PD and demonstrating its modulation by DBS, this important work also lays to the foundation for further studies in DBS patients employing similar techniques.
1. Canolty RT, Knight RT. The functional role of cross-frequency coupling. Trends Cogn Sci (Regul Ed). 2010;14(11):506–515.
2. de Hemptinne C, Ryapolova-Webb ES, Air EL, et al.. Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci USA. 2013;110(12):4780–4785.