Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's Disease

Abstract

Oscillations in neural activity play a critical role in neural computation and communication. There is intriguing new evidence that the nonsinusoidal features of the oscillatory waveforms may inform underlying physiological and pathophysiological characteristics. Time-domain waveform analysis approaches stand in contrast to traditional Fourier-based methods, which alter or destroy subtle waveform features. Recently, it has been shown that the waveform features of oscillatory beta (13-30 Hz) events, a prominent motor cortical oscillation, may reflect near-synchronous excitatory synaptic inputs onto cortical pyramidal neurons. Here we analyze data from invasive human primary motor cortex (M1) recordings from patients with Parkinson's disease (PD) implanted with a deep brain stimulator (DBS) to test the hypothesis that the beta waveform becomes less sharp with DBS, suggesting that M1 input synchrony may be decreased. We find that, in PD, M1 beta oscillations have sharp, asymmetric, nonsinusoidal features, specifically asymmetries in the ratio between the sharpness of the beta peaks compared with the troughs. This waveform feature is nearly perfectly correlated with beta-high gamma phase-amplitude coupling ( = 0.94), a neural index previously shown to track PD-related motor deficit. Our results suggest that the pathophysiological beta generator is altered by DBS, smoothing out the beta waveform. This has implications not only for the interpretation of the physiological mechanism by which DBS reduces PD-related motor symptoms, but more broadly for our analytic toolkit in general. That is, the often-overlooked time-domain features of oscillatory waveforms may carry critical physiological information about neural processes and dynamics. To better understand the neural basis of cognition and disease, we need to understand how groups of neurons interact to communicate with one another. For example, there is evidence that parkinsonian bradykinesia and rigidity may arise from an oversynchronization of afferents to the motor cortex, and that these symptoms are treatable using deep brain stimulation. Here we show that the waveform shape of beta (13-30 Hz) oscillations, which may reflect input synchrony onto the cortex, is altered by deep brain stimulation. This suggests that mechanistic inferences regarding physiological and pathophysiological neural communication may be made from the temporal dynamics of oscillatory waveform shape.

Distinct Subthalamic Coupling in the ON State Describes Motor Performance in Parkinson's Disease

“…Coupling in the motor cortex between beta phase and broadband gamma (50–200 Hz) amplitude was reported previously by de Hemptinne and colleagues . Yet, recent studies have suggested that this coupling could have originated from the harmonics of nonsinusoidal sharp‐edged beta‐band activity . The HFO activity we observed, however, does not appear as a broadband signal.…”

Changes in neuronal activity of cortico‐basal ganglia–thalamic networks induced by acute dopaminergic manipulations in rats

“…Moreover, a strict division between the analyses of rate and rhythmicity in cell firing may in itself be misleading. In simulations of activity patterns arising in cortex as a consequence of modifications of input from external sources, it has been shown that cortical beta oscillations could in fact be induced by transient rate changes in thalamocortical projections [Sherman et al, 2016; also discussed in a recent study on beta oscillations in PD patients (Cole et al, 2017)]. Intriguingly, the transient bouts of synchronized activity observed in our experiments (see Fig.…”

“…Examining the beta power increase in the temporal domain revealed that this activity was typically not characterized by a stable oscillatory state, but instead stemmed from transient spindle‐like activity which is also characterized by a difference in peak sharpness between peaks and troughs (Fig. B; see also Cole et al ., ; Dejean et al ., ; Halje et al ., ; Yael et al ., ; Yang et al ., ). It should, however, be pointed out that the observed increase in low‐frequency LFP power in this brain structure, in this experiment, did not temporally match the onset of catalepsy (which started already ~20 min after injection of D1/D2R antagonists and remained throughout the recording session).…”

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

“…Perhaps more complex functional interactions, such as cross‐frequency coupling (see also, (Tewarie et al, )), could play a role in the pathophysiology of PD motor symptoms. Cross‐frequency coupling was previously found within the STN (van Wijk et al, ) and within the motor cortex ((de Hemptinne et al, ), but see also (Cole et al, )) but not between these two structures.…”