Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.
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SUBMITTER: Wiest C
PROVIDER: S-EPMC7115855 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesUnilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) improves ipsilateral symptoms, but how this occurs is not well understood. We investigated whether unilateral STN DBS suppresses contralateral STN beta activity in the local field potential (LFP), since previous research has shown that activity in the beta band can correlate with the severity of contralateral clinical symptoms and is modulated by DBS.Materials and methodsWe recorded STN LFPs from 14 patients who underwent bilateral STN DBS for PD. Following a baseline recording, unilateral STN stimulation was delivered at therapeutic parameters while LFPs were recorded from the contralateral (unstimulated) STN.ResultsUnilateral STN DBS suppressed contralateral beta power (p = 0.039, relative suppression = -5.7% ± [SD] 16% when averaging across the highest beta peak channels; p = 0.033, relative suppression = -5.2% ± 13% when averaging across all channels). Unilateral STN DBS produced a 17% ipsilateral (p = 0.016) and 29% contralateral (p = 0.002) improvement in upper limb hemi-body bradykinesia-rigidity (UPDRS-III, items 3.3-3.6). The ipsilateral clinical improvement and the change in contralateral beta power were not significantly correlated.ConclusionsUnilateral STN DBS suppresses contralateral STN beta LFP. This indicates that unilateral STN DBS modulates bilateral basal ganglia networks. It remains unclear whether this mechanism accounts for the ipsilateral motor improvements.
| S-EPMC7299664 | biostudies-literature
Project description:Background:Directional deep brain stimulation (DBS) technology aims to address the limitations, such as stimulation-induced side effects, by delivering selective, focal modulation via segmented contacts. However, DBS programming becomes more complex and time-consuming for clinical feasibility. Local field potentials (LFPs) might serve a functional role in guiding clinical programming. Objective:In this pilot study, we investigated the spectral dynamics of directional LFPs in subthalamic nucleus (STN) and their relationship to motor symptoms of Parkinson's disease (PD). Methods:We recorded intraoperative STN-LFPs from 8-contact leads (Infinity-6172, Abbott Laboratories, Illinois, United States) in 8 PD patients at rest. Directional LFPs were referenced to their common average and time-frequency analysis was computed using a modified Welch periodogram method. The beta band (13-35 Hz) features were extracted and their correlation to preoperative UPDRS-III scores were assessed. Results:Normalized beta power (13-20 Hz) and normalized peak power (13-35 Hz) were found to be higher in anterior direction despite lack of statistical significance (p > 0.05). Results of the Spearman correlation analysis demonstrated positive trends with bradykinesia/rigidity in dorsoanterior direction (r = 0.659, p = 0.087) and with axial scores in the dorsomedial direction (r = 0.812, p = 0.072). Conclusion:Given that testing all possible combinations of contact pairs and stimulation parameters is not feasible in a single clinic visit, spatio-spectral LFP dynamics obtained from intraoperative recordings might be used as an initial marker to select optimal contact(s).
| S-EPMC7198898 | biostudies-literature
Project description:BackgroundDeep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD.MethodsThirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months.ResultsAs hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient.ConclusionsThis study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
| S-EPMC4103427 | biostudies-literature
Project description:Segmented deep brain stimulation leads feature directional electrodes that allow for a finer spatial control of electrical stimulation compared to traditional ring-shaped electrodes. These segmented leads have demonstrated enlarged therapeutic windows and have thus the potential to improve the treatment of Parkinson's disease patients. Moreover, they provide a unique opportunity to record directional local field potentials. Here, we investigated whether directional local field potentials can help identify the best stimulation direction to assist device programming. Four Parkinson's disease patients underwent routine implantation of the subthalamic nucleus. Firstly, local field potentials were recorded in three directions for two conditions: In one condition, the patient was at rest; in the other condition, the patient's arm was moved. Secondly, current thresholds for therapeutic and side effects were identified intraoperatively for directional stimulation. Therapeutic windows were calculated from these two thresholds. Thirdly, the spectral power of the total beta band (13-35 Hz) and its sub-bands low, high, and peak beta were analyzed post hoc. Fourthly, the spectral power was used by different algorithms to predict the ranking of directions. The spectral power profiles were patient-specific, and spectral peaks were found both in the low beta band (13-20 Hz) and in the high beta band (20.5-35 Hz). The direction with the highest spectral power in the total beta band was most indicative of the 1st best direction when defined by therapeutic window. Based on the total beta band, the resting condition and the moving condition were similarly predictive about the direction ranking and classified 83.3% of directions correctly. However, different algorithms were needed to predict the ranking defined by therapeutic window or therapeutic current threshold. Directional local field potentials may help predict the best stimulation direction. Further studies with larger sample sizes are needed to better distinguish the informative value of different conditions and the beta sub-bands.
| S-EPMC7556345 | biostudies-literature
Project description:Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.
| S-EPMC3413674 | biostudies-literature
Project description:Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in alleviating movement disability in patients with Parkinson’s disease (PD). However, its therapeutic mechanism of action is unknown. The healthy striatum exhibits rich dynamics resulting from an interaction of beta, gamma, and theta oscillations. These rhythms are essential to selection and execution of motor programs, and their loss or exaggeration due to dopamine (DA) depletion in PD is a major source of behavioral deficits. Restoring the natural rhythms may then be instrumental in the therapeutic action of DBS. We develop a biophysical networked model of a BG pathway to study how abnormal beta oscillations can emerge throughout the BG in PD and how DBS can restore normal beta, gamma, and theta striatal rhythms. Our model incorporates STN projections to the striatum, long known but understudied, found to preferentially target fast-spiking interneurons (FSI). We find that DBS in STN can normalize striatal medium spiny neuron activity by recruiting FSI dynamics and restoring the inhibitory potency of FSIs observed in normal conditions. We also find that DBS allows the reexpression of gamma and theta rhythms, thought to be dependent on high DA levels and thus lost in PD, through cortical noise control. Our study highlights that DBS effects can go beyond regularizing BG output dynamics to restoring normal internal BG dynamics and the ability to regulate them. It also suggests how gamma and theta oscillations can be leveraged to supplement DBS treatment and enhance its effectiveness.
| S-EPMC9171607 | biostudies-literature
Project description:Objective.The electrode-tissue interface surrounding a deep brain stimulation (DBS) lead is known to be highly dynamic following implantation, which may have implications on the interpretation of intraoperatively recorded local field potentials (LFPs). We characterized beta-band LFP dynamics following implantation of a directional DBS lead in the sensorimotor subthalamic nucleus (STN), which is a primary target for treating Parkinson's disease.Approach.Directional STN-DBS leads were implanted in four healthy, non-human primates. LFPs were recorded over two weeks and again 1-4 months after implantation. Impedance was measured for two weeks post-implant without stimulation to compare the reactive tissue response to changes in LFP oscillations. Beta-band (12-30 Hz) peak power was calculated from the LFP power spectra using both common average referencing (CAR) and intra-row bipolar referencing (IRBR).Results.Resting-state LFPs in two of four subjects revealed a steady increase of beta power over the initial two weeks post-implant whereas the other two subjects showed variable changes over time. Beta power variance across days was significantly larger in the first two weeks compared to 1-4 months post-implant in all three long-term subjects. Further, spatial maps of beta power several hours after implantation did not correlate with those measured two weeks or 1-4 months post-implant. CAR and IRBR beta power correlated across short- and long-term time points. However, depending on the time period, subjects showed a significant bias towards larger beta power using one referencing scheme over the other. Lastly, electrode-tissue impedance increased over the two weeks post-implant but showed no significant correlation to beta power.Significance.These results suggest that beta power in the STN may undergo significant changes following DBS lead implantation. DBS lead diameter and electrode recording configurations can affect the post-implant interpretation of oscillatory features. Such insights will be important for extrapolating results from intraoperative and externalized LFP recordings.
| S-EPMC8504120 | biostudies-literature
Project description:Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process.
| S-EPMC5006230 | biostudies-literature
Project description:Objective: To observe the efficacy of bilateral subthalamic nucleus deep brain stimulation on Pisa syndrome in patients with Parkinson's disease. Methods: A total of 52 patients with Parkinson's disease who underwent deep brain stimulation in Beijing Hospital from July 1, 2016 to July 1, 2020 were reviewed. The clinical data were collected for the patients who met the diagnostic criteria of Pisa syndrome on "Medication-Off" state pre-operatively. Results: Two patients met the diagnostic criteria of Pisa syndrome before operation, with a Pisa angle of 10 and 14°, respectively. The lateral trunk flexion of the two patients improved after operation. In stimulation-on/medication-off state, the Pisa angle decreased from 10 to 2° and from 14 to 6°, respectively. Conclusion: Bilateral subthalamic nucleus deep brain stimulation might have beneficial effects on lateral trunk flexion in PD patients, but the predictors of curative effect are not clear.
| S-EPMC8566818 | biostudies-literature
Project description:Apathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta-analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre- and post-DBS or the cross-sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty-three articles were included in the meta-analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre-operatively (g = 0.34, 95% confidence interval [CI] = 0.19-0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03-0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta-analysis indicate that apathy is increased after STN DBS compared to the pre-operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC7986158 | biostudies-literature