Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats.

JOURNAL/nrgr/04.03/01300535-202504000-00031/figure1/v/2024-07-06T104127Z/r/image-tiff Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson's disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Subthalamic nucleus dynamics track microlesion effect in Parkinson's disease.

Parkinson's Disease (PD) is characterized by the temporary alleviation of motor symptoms following electrode implantation (or nucleus destruction), known as the microlesion effect (MLE). Electrophysiological studies have explored different PD stages, but understanding electrophysiological characteristics during the MLE period remains unclear. The objective was to examine the characteristics of local field potential (LFP) signals in the subthalamic nucleus (STN) during the hyperacute period following implantation (within 2 days) and 1 month post-implantation. 15 patients diagnosed with PD were enrolled in this observational study, with seven simultaneous recordings of bilateral STN-LFP signals using wireless sensing technology from an implantable pulse generator. Recordings were made in both on and off medication states over 1 month after implantation. We used a method to parameterize the neuronal power spectrum to separate periodic oscillatory and aperiodic components effectively. Our results showed that beta power exhibited a significant increase in the off medication state 1 month after implantation, compared to the postoperative hyperacute period. Notably, this elevation was effectively attenuated by levodopa administration. Furthermore, both the exponents and offsets displayed a decrease at 1 month postoperatively when compared to the hyperacute postoperative period. Remarkably, levodopa medication exerted a modulatory effect on these aperiodic parameters, restoring them back to levels observed during the hyperacute period. Our findings suggest that both periodic and aperiodic components partially capture distinct electrophysiological characteristics during the MLE. It is crucial to adequately evaluate such discrepancies when exploring the mechanisms of MLE and optimizing adaptive stimulus protocols.

The effect of aperiodic components in distinguishing Alzheimer's disease from frontotemporal dementia.

Distinguishing between Alzheimer's disease (AD) and frontotemporal dementia (FTD) presents a clinical challenge. Inexpensive and accessible techniques such as electroencephalography (EEG) are increasingly being used to address this challenge. In particular, the potential relevance between aperiodic components of EEG activity and these disorders has gained interest as our understanding evolves. This study aims to determine the differences in aperiodic activity between AD and FTD and evaluate its potential for distinguishing between the two disorders. A total of 88 participants, including 36 patients with AD, 23 patients with FTD, and 29 healthy controls (CN) underwent cognitive assessment and scalp EEG acquisition. Neuronal power spectra were parameterized to decompose the EEG spectrum, enabling comparison of group differences in different components. A support vector machine was employed to assess the impact of aperiodic parameters on the differential diagnosis. Compared with the CN group, both the AD and FTD groups showed varying degrees of increased alpha power (both periodic and raw power) and theta alpha power ratio. At the channel level, theta power (both periodic and raw power) in the frontal regions was higher in the AD group compared to the FTD group, and aperiodic parameters (both exponents and offsets) in the frontal, temporal, central, and parietal regions were higher in the AD group than in the FTD group. Importantly, the inclusion of aperiodic parameters led to improved performance in distinguishing between the two disorders. These findings highlight the significance of aperiodic components in discriminating dementia-related diseases.

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats.

AIM: Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. METHODS: Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. RESULTS: We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. CONCLUSION: Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.

Separating the aperiodic and periodic components of neural activity in Parkinson's disease.

Most studies on electrophysiology have not separated aperiodic activity from the spectra but have rather evaluated a combined periodic oscillatory component and the aperiodic component. As the understanding of aperiodic activity gradually deepens, its potential physiological significance has acquired increased appreciation. Herein, we investigated the two components in scalp electroencephalogram in 16 healthy controls and 15 patients with Parkinson's disease (PD); the results revealed that aperiodic parameters were approximately symmetrically distributed in topography in patients with PD and were significantly modulated by dopaminergic medication in channels C4, C3, CP5 and FC5. In sum, our findings might provide indicators for evaluating treatment response in PD and highlight the importance of re-evaluating the neuronal power spectra parameterization.

α and θ oscillations in the subthalamic nucleus are potential biomarkers for Parkinson's disease with depressive symptoms.

INTRODUCTION: Abnormal α oscillations in the bed nucleus of stria terminalis and subgenual cingulate of patients with depression correlate with symptom severity. Some Parkinson's disease (PD) patients also have abnormal θ-α oscillations in the subthalamic nucleus (STN). However, the relationship between abnormal θ-α oscillations and depressive symptoms in PD patients has not been determined. This study explored the correlation between α and θ oscillations of the STN and depressive symptoms in PD patients. METHODS: We conducted a retrospective case-control study on 36 PD patients with (dPD group) or without depressive symptoms (nPD group), analyzing the difference in the average power spectral density (PSD) of α and θ oscillations of the local field potential (LFP) recorded in the STN during deep brain stimulation (DBS), and their correlation with the Hamilton depression rating scale (HAMD) of PD patients during the same period. RESULTS: The dPD group had a higher PSD of α oscillations and a lower PSD of θ oscillations in the left ventral STN. The PSD of α oscillations of the left ventral STN were positively correlated with the severity of depressive symptoms, whereas the PSD of θ oscillations of this location was negatively correlated with severity of depressive symptoms. The PSD of α and θ oscillations did not correlate with motor symptoms, sleep quality, or quality of life score. CONCLUSION: Abnormal α and θ oscillations of the left ventral STN could be used as biomarkers of PD with depressive symptoms, which might guide STN-DBS treatment.