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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]

Background: Pedunculopontine nucleus (PPN) DBS has emerged as a potential intervention for patients with gait and balance disorders. However, targeting this nucleus can be challenging. We report on the first neuropathological analyses after PPN-DBS surgery in advanced progressive supranuclear palsy (PSP). Methods: Two patients with PSP underwent unilateral PPN-DBS surgery and were clinically followed to autopsy. Both patients underwent postmortem neuropathological analysis, including choline acetyltransferase immunohistochemistry, to ascertain PPN boundaries and electrode location. Results: Both patients experienced partial improvement in some motor and nonmotor domains postintervention, but died shortly of other complications. Postmortem neuropathological analysis of each patient confirmed the electrode in a region of cholinergic neuronal loss corresponding to the PPN. Conclusions: We provide histopathological evidence for the validity of our stereotactic approach to target the PPN and correlate electrode location with clinical outcomes. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Despite improvements in anatomic imaging of the basal ganglia, microelectrode recording is still an invaluable tool in locating appropriate targets for neurosurgical intervention. These recording also provide an unparalleled opportunity to study the pathophysiological aspects of diseases. This article reviews the principles of microelectrode recording in functional neurosurgery and discusses the pathologic neurophysiologic findings commonly encountered. It also highlights some of the potential mechanisms of action of both dopaminergic drugs and deep brain stimulation. In addition we review the recent work on pedunculopontine nucleus neurophysiology and trials of deep brain stimulation in that region for gait disturbances in Parkinson's disease. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Subthalamic nucleus deep brain stimulation (STN-DBS) is effective in advanced Parkinson's disease (PD), but its effects on the levodopa response are unclear. We studied the levodopa response after long-term STN-DBS, STN-DBS efficacy and predictive value of preoperative levodopa response to long-term DBS benefit in 33 PD patients with bilateral STN-DBS. Patients were assessed using the Unified Parkinson's Disease Rating Scale preoperatively (with and without medications) and postoperatively (without medications or stimulation, with only medications or stimulation, and with both medications and stimulation). Levodopa response significantly decreased postoperatively by 31.1% at 3 years and 32.3% at 5 years, possibly related to the reduction in medication requirement, direct STN stimulation effect or PD progression. STN-DBS alone significantly improved motor scores (37.2% at 3 years and 35.1% at 5 years) and activities of daily living scores (27.1% at 3 years and 19.2% at 5 years). Anti-PD drugs were significantly reduced by 47.9% at 3 years and 39.8% at 5 years. However, the magnitude of the preoperative response to levodopa did not predict DBS benefit at 3 and 5 years. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being evaluated as a potential new therapy for patients with Huntington's disease (HD). In addition to skeletal movement disorders, HD patients have difficulty initiating voluntary saccades and have difficulty in suppressing rapid saccades toward newly appearing stimuli. We measured several saccade parameters in an HD patient who had marked improvement of clinical symptoms with bilateral GPi DBS to determine whether oculomotor performance improved in parallel with clinical scores. Oculomotor performance was assessed using three testing paradigms: pro-saccades, anti-saccades, and memory-guided saccades. The data from the HD patient was also compared to that of two healthy controls. Pallidal DBS decreased pro-saccade latency, total movement time, and the number of correctly executed trials, as well as increasing saccade gain. Memory-saccade performance was negatively affected with stimulation: saccade gain decreased, latency increased, and the patient's ability to suppress unwanted saccades decreased with stimulation. Our data demonstrate a task-specific improvement of oculomotor deficits in this HD patient with pallidal DBS, supporting a role of GPi in oculomotor control. © 2004 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA. © 2004 Movement Disorder Society [ABSTRACT FROM AUTHOR]