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Background: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. Objectives: The study aimed to characterize the long‐term effects of STN–deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. Methods: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN‐LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular‐resampling auto‐spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN‐LFP signals in beta band. Results: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. Conclusions: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma‐aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long‐term STN‐DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's disease might develop treatment‐resistant axial dysfunction after bilateral subthalamic stimulation. Objectives: To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. Methods: Randomized, double‐blinded, double‐crossover trial. Results: In 22 participants (51–79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left‐sided amplitude resulted in a 2.5‐point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) (P = 0.005, uncorrected) and a 1.9‐point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). Conclusions: Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment‐resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disease affecting the supply of dopamine to basal ganglia nuclei, leading to pathological beta band (13–35 Hz) oscillations in the subthalamic nucleus (STN). STN and beta activity are recognized in motoric functions but their role in cognitive functions remains elusive. We examined single unit and beta local field potential (LFP) activity in the STN during a visual choice preference task in PD patients (n = 12) undergoing deep brain stimulation surgery. Patients viewed 2 of 5 possible animal picture‐pairs and were instructed to choose their favorite ("fav") picture by clicking the left or right mouse key. A block of trials consisted of 50–75 picture‐pair presentations. Single unit histograms and LFP spectrograms were aligned to picture presentation and point of decision for pairs that included the fav and non‐fav pictures, respectively. A total of 58 neurons from 26 blocks of trials were analyzed. Thirty of 58 neurons showed a selective change in spiking activity 0.20–0.65 s to fav picture presentation, which preceded the shortest recorded reaction time (=0.7 s), and 17/58 neurons showed no significant response in our task. Beta LFP significantly desynchronized in response to fav but not non‐fav pictures in all trials, and in 14/26 blocks of trials, the desynchronization was followed by a "beta burst" and ramp‐up to baseline activity. Neurons with choice preference responses were found throughout the dorsoventral extent of the STN. STN single units and beta activity are modulated during visual choice preference, and this suggests a role for STN beta activity in cognitive processing. [ABSTRACT FROM AUTHOR]

Objective: Many lines of evidence suggest that response conflict recruits brain regions in the cortical-basal ganglia system. Within the basal ganglia, deep brain recordings from the subthalamic nucleus (STN) have shown that conflict triggers a transient increase in low-frequency oscillations (LFOs; 2-8Hz). Here, we deployed a new method of delivering short trains of event-related deep brain stimulation (DBS) to the STN to test the causal role of the STN and its associated circuits in conflict-related processing.Methods: In a double-blind design, we stimulated the STN in patients with Parkinson disease by locking brief trains of DBS to specific periods of the trial within a Stroop task.Results: Stimulation had a specific effect on conflict compared to nonconflict trials by relatively speeding responses on conflict trials (ie, reducing the Stroop effect, defined as the difference in reaction time between conflict and nonconflict trials) when it was delivered in the preresponse period in the preparation phase. Stimulation also increased errors when it was delivered early in the response window. This latter result corresponded to the timing of the conflict-induced increase in LFOs observed in the absence of stimulation but was not directly related to the reduction in the Stroop effect.Interpretation: These results support the theory that the time of LFO increase recorded from the STN corresponds to a conflict-processing function. They also provide one of the first demonstrations of event-related DBS of the STN in humans during a cognitive control paradigm. Ann Neurol 2018;84:515-526. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus ( STN) deep-brain stimulation ( DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording ( MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke-Vitek methodology and local field potential ( LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike-oscillations analysis(beta peak, P = 0.4; signal-to-noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high-dose dexmedetomidine should be avoided during DBS surgery. [ABSTRACT FROM AUTHOR]