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Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear., Objective: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment., Methods: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy., Results: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations., Conclusions: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson's Disease (PD)., Methods: The resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms., Results: The proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia., Conclusions: This study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD., Significance: This study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised., Methods: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings., Results: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz)., Conclusions: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aims to use the activities recorded directly from the deep brain stimulation (DBS) electrode to address the focality and distinct nature of the local field potential (LFP) activities of different frequency., Methods: Pre-operative and intra-operative magnetic resonance imaging (MRI) were acquired from patients with Parkinson's disease (PD) who underwent DBS in the subthalamic nucleus and intra-operative LFP recording at rest and during cued movements. Images were reconstructed and 3-D visualized using Lead-DBS® toolbox to determine the coordinates of contact. The resting spectral power and movement-related power modulation of LFP oscillations were estimated., Results: Both subthalamic LFP activity recorded at rest and its modulation by movement had focal maxima in the alpha, beta and gamma bands. The spatial distribution of alpha band activity and its modulation was significantly different to that in the beta band. Moreover, there were significant differences in the scale and timing of movement related modulation across the frequency bands., Conclusion: Subthalamic LFP activities within specific frequency bands can be distinguished by spatial topography and pattern of movement related modulation., Significance: Assessment of the frequency, focality and pattern of movement related modulation of subthalamic LFPs reveals a heterogeneity of neural population activity in this region. This could potentially be leveraged to finesse intra-operative targeting and post-operative contact selection., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN., Methods: Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states., Results: Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11-20Hz) range was attenuated in medicated PD., Conclusion: The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The effect of deep brain stimulation(DBS)surgery treatment for Parkinson’s disease is determined by the accuracy of the electrodes placement and localization.The subthalamic nuclei(STN)as the implant target is small and has no clear boundary on the images.In addition,the intra-operative magnetic resonance images(MRI)have such a low resolution that the artifacts of the electrodes impact the observation.The three-dimensional(3D)visualization of STN and other nuclei nearby is able to provide the surgeons with direct and accurate localizing information.In this study,pre-and intra-operative MRIs of the Parkinson’s disease patients were used to realize the 3Dvisualization.After making a co-registration between the high-resolution pre-operative MRIs and the low-resolution intraoperative MRIs,we normalized the MRIs into a standard atlas space.We used a special threshold mask to search the lead trajectories in each axial slice.After checking the location of the electrode contacts with the coronal MRIs of the patients,we reconstructed the whole lead trajectories.Then the STN and other nuclei nearby in the standard atlas space were visualized with the grey images of the standard atlas,accomplishing the lead reconstruction and nerve nuclei visualization near STN of all patients.This study provides intuitive and quantitative information to identify the accuracy of the DBS electrode implantation,which could help decide the post-operative programming setting.

The dysfunction of subthalamic nucleus is the main cause of Parkinson's disease. Local field potentials in human subthalamic nucleus contain rich physiological information. The present study aimed to quantify the oscillatory and dynamic characteristics of local field potentials of subthalamic nucleus, and their modulation by the medication therapy for Parkinson's disease. The subthalamic nucleus local field potentials were recorded from patients with Parkinson's disease at the states of on and off medication. The oscillatory features were characterised with the power spectral analysis. Furthermore, the dynamic features were characterised with time-frequency analysis and the coefficient of variation measure of the time-variant power at each frequency. There was a dominant peak at low beta-band with medication off. The medication significantly suppressed the low beta component and increased the theta component. The amplitude fluctuation of neural oscillations was measured by the coefficient of variation. The coefficient of variation in 4-7 Hz and 60-66 Hz was increased by medication. These effects proved that medication had significant modulation to subthalamic nucleus neural oscillatory synchronization and dynamic features. The subthalamic nucleus neural activities tend towards stable state under medication. The findings would provide quantitative biomarkers for studying the mechanisms of Parkinson's disease and clinical treatments of medication or deep brain stimulation.

Pathological neural activity in subthalamic nucleus (STN) is closely related to the symptoms of Parkinson' s disease. Local field potentials (LFPs) recordings from subthalamic nucleus show that power spectral peaks exist at tremor, double tremor and tripble tremor frequencies, respectively. The interaction between these components in the multi-frequency tremor may be related to the generation of tremor. To study the linear and nonlinear relationship between those components, we analyzed STN LFPs from 9 Parkinson's disease patients using time frequency, cross correlation, Granger casuality and bi-spectral analysis. Results of the time-frequency analysis and cross-frequency correlation analysis demonstrated that the power density of those components significantly decreased as the alleviation of tremor and cross-correlation (0.18-0.50) exists during tremor period. Granger causality of the time-variant amplitude showed stronger contribution from tremor to double tremor components, and contributions from both tremor and double tremor components to triple tremor component. Quadratic phase couplings among these three components were detected by the bispectral approaches. The linear and nonlinear relationships existed among the multi-components and certainly confirmed that the dependence cross those frequencies and neurological mechanism of tremor involved complicate neural processes.

Neuronal activity within and across the cortex and basal ganglia is pathologically synchronized, particularly at approximately 20 Hz in patients with Parkinson's disease. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes like Parkinson's disease. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus (STN) at various frequencies between 5 and 30 Hz in two cohorts of eight patients with Parkinson's disease from two different surgical centres. We found that evoked activity consisted of a series of diminishing waves with a peak latency of 21 ms for the first wave in the series. The cortical evoked potentials (cEPs) averaged in each group were well fitted by a damped oscillator function (r > or = 0.9, P < 0.00001). Fits suggested that the natural frequency of the subthalamo-cortical circuit was around 20 Hz. When the system was forced at this frequency by stimulation of the STN at 20 Hz, the undamped amplitude of the modelled cortical response increased relative to that with 5 Hz stimulation in both groups (P < or = 0.005), consistent with resonance. Restoration of dopaminergic input by treatment with levodopa increased the damping of oscillatory activity (as measured by the modelled damping factor) in both patient groups (P < or = 0.001). The increased damping would tend to limit resonance, as confirmed in simulations. Our results show that the basal ganglia-cortical network involving the STN has a tendency to resonate at approximately 20 Hz in Parkinsonian patients. This resonance phenomenon may underlie the propagation and amplification of activities synchronized around this frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia-cortical network.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.