Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson’s disease

Abstract

Bradykinesia is a cardinal motor symptom in Parkinson's disease (PD), the pathophysiology of which is not fully understood. We analyzed the role of cross-frequency coupling of oscillatory cortical activity in motor impairment in PD patients and healthy controls. High-density EEG signals were recorded during various motor activities and at rest. Patients performed a repetitive finger pressing task normally, but were slower than controls during tapping. Phase-amplitude coupling (PAC) between β (13-30Hz) and broadband γ (50-150Hz) was computed from individual EEG source signals in the premotor, primary motor, and primary somatosensory cortices, and the primary somatosensory complex. In all four regions, averaging the entire movement period resulted in higher PAC in patients than in controls for the resting condition and the pressing task (similar performance between groups). However, this was not the case for the tapping tasks where patients performed slower. This suggests the strength of state-related β-γ PAC does not determine Parkinsonian bradykinesia. Examination of the dynamics of oscillatory EEG signals during motor transitions revealed a distinctive motif of PAC rise and decay around press onset. This pattern was also present at press offset and slow tapping onset, linking such idiosyncratic PAC changes to transitions between different movement states. The transition-related PAC modulation in patients was similar to controls in the pressing task but flattened during slow tapping, which related to normal and abnormal performance, respectively. These findings suggest that the dysfunctional evolution of neuronal population dynamics during movement execution is an important component of the pathophysiology of Parkinsonian bradykinesia.

Temporal Ablation of Primary Cilia Impairs Brainwave Patterns Implicated in Memory Formation

“…It was found that phase-amplitude coupling (PAC) between the theta and high-gamma frequencies was impaired in awake and in non-REM sleep of inducible IFT88 KO mice. PAC, specifically between the theta-gamma bandwidths, has a well-established role in memory formation and is known to be disrupted in humans afflicted with mild cognitive impairment, Alzheimer’s, and Parkinson’s [25], [44][45]. Based off these data we can postulate that inducible IFT88 KO mice will have impaired memory formation, which has been recorded in preliminary behavioral experiments [46].…”

Beta–Gamma Phase-Amplitude Coupling as a Non-Invasive Biomarker for Parkinson’s Disease: Insights from Electroencephalography Studies

“…Currently, five studies (for more details, please see Table 1 ) present findings of EEG-detected beta–gamma PAC in Parkinson’s disease, providing reliable groundwork for exploring the role of PAC in PD pathology [ 13 , 16 , 17 , 34 , 50 ]. Three of these studies present data from resting state recordings [ 16 , 34 , 50 ], one provides a comparison of resting state and movement recordings [ 17 ], and one presents data from recordings made during repetitive movements [ 13 ].…”

“…Several electrophysiological changes have been associated with PD [ 12 ]. An increase in phase-amplitude coupling (PAC) between the beta and gamma bands detected over the motor cortex has been associated with motor abnormalities of PD [ 13 , 14 ]. PAC is a form of cross-frequency coupling ( Figure 1 ), a crucial mechanism for information processing in the brain.…”

“…Furthermore, the primate model reveals PAC strength increases during sleep; however, it is not indicative of Parkinsonism in the unconscious state [ 48 ]. Studies show that PAC can be modulated by movement and responds to different movement types [ 13 , 17 ]. Changes in PAC during movement have also been applied to differentiate PD patients from healthy participants, which has been confirmed in studies investigating PAC modulation during unilateral hand movements [ 13 , 49 ] or during walking [ 18 ].…”

Assess stimulation-induced dyskinesia and its potential physiological mechanism using phase-amplitude coupling

“…To be noted, a number of theoretical theories and laboratory results has shown the significance of interactions between activities occurring at various frequencies, especially in processing and transmissing information. However, to find the exact relationship between different frequency bandwidth require methods different from the traditional way of processing information such as wavelet convolution or STFT, which always focus on the independent oscillatory activity and therefore very hard to show the relationship between different frequency bands and even across different neural nucleus, as shown in the figure2 [8]. The coupling between theta and gamma in the hippocampus of rodents is one of the most well-studied examples of cross-frequency coupling (CFC).…”