Cortical network organization reflects clinical response to subthalamic nucleus deep brain stimulation in Parkinson's disease.
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SUBMITTER: Bockova M
PROVIDER: S-EPMC8559467 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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:BackgroundWhilst MRI guided Focused Ultrasound (MRgFUS) thalamotomy is an effective treatment option for tremor disorders, there are reports of tremor recurrence in patients with tremor dominant Parkinson's disease (PD). The mechanisms for tremor recurrence are unknown but likely relate to the duality of tremor network pathways with ramifications for subsequent treatment options.CasesWe report two cases of tremor dominant PD who experienced tremor recurrence following MRgFUS thalamotomy with subsequent successful subthalamic nucleus deep brain stimulation (DBS). Tremor scores were measured at baseline, 1- and 3-months post MRgFUS and at least 18 months post DBS in both patients. Both cases evidenced immediate improvement in tremor, after MRgFUS, followed by subsequent tremor recurrence. STN DBS resulted in almost complete long-term tremor alleviation in both cases.ConclusionsThese cases demonstrate the efficacy and feasibility of STN DBS in patients with tremor dominant PD with tremor recurrence following MRgFUS thalamotomy. We discuss the dualism of tremor outflow pathways that may have implications for single target lesional therapies.
| S-EPMC10026293 | biostudies-literature
Project description:ObjectivesFirstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.MethodsHigh angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.ResultsAll patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.InterpretationThese findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
| S-EPMC6581538 | 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
Project description:The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.
| S-EPMC9532054 | biostudies-literature
Project description:Both subthalamic nucleus (STN) and caudal zona incerta (cZI) have been implicated as the optimal locus for deep brain stimulation (DBS) in Parkinson's disease (PD). We present a retrospective clinico-anatomical analysis of outcomes from DBS targeting both STN and cZI. Forty patients underwent bilateral DBS using an image-verified implantable guide tube/stylette technique. Contacts on the same quadripolar lead were placed in both STN and cZI. After pulse generator programming, contacts yielding the best clinical effect were selected for chronic stimulation. OFF-medication unified PD rating scale (UPDRS) part III scores pre-operatively and ON-stimulation at 1-2 year follow up were compared. Active contacts at follow-up were anatomically localised from peri-operative imaging. Overall, mean UPDRS part III score improvement was 55?±?9% (95% confidence interval), with improvement in subscores for rigidity (59?±?13%), bradykinesia (58?±?13%), tremor (71?±?24%) and axial features (36?±?19%). Active contacts were distributed in the following locations: (1) within posterior/dorsal STN (50%); (2) dorsal to STN (24%); (3) in cZI (21%); and (4) lateral to STN (5%). When contacts were grouped by location, no significant differences between groups were seen in baseline or post-operative improvement in contralateral UPDRS part III subscores. We conclude that when both STN and cZI are targeted, active contacts are distributed most commonly within and immediately dorsal to STN. In a subgroup of cases, cZI contacts were selected for chronic stimulation in preference. Dual targeting of STN and cZI is feasible and may provide extra benefit compared with conventional STN DBS is some patients.
| S-EPMC6704060 | biostudies-literature
Project description:This study compares the effects on motor symptoms between conventional deep brain stimulation (cDBS) and closed-loop adaptive deep brain stimulation (aDBS) in patients with Parkinson's Disease. The aDBS stimulation is controlled by the power in the beta band (12-35 Hz) of local field potentials recorded directly by subthalamic nucleus electrodes. Eight subjects were assessed in two 8-h stimulation sessions (first day, cDBS; second day, aDBS) with regular levodopa intake and during normal daily activities. The Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, the Rush scale for dyskinesias, and the total electrical energy delivered to the tissues per second (TEEDs) were significantly lower in the aDBS session (relative UPDRS mean, cDBS: 0.46 ± 0.05, aDBS: 0.33 ± 0.04, p = 0.015; UPDRS part III rigidity subset mean, cDBS: 2.9143 ± 0.6551 and aDBS: 2.1429 ± 0.5010, p = 0.034; UPDRS part III standard deviation cDBS: 2.95, aDBS: 2.68; p = 0.047; Rush scale, cDBS 2.79 ± 0.39 versus aDBS 1.57 ± 0.23, p = 0.037; cDBS TEEDs mean: 28.75 ± 3.36 µj s-1, aDBS TEEDs mean: 16.47 ± 3.33, p = 0.032 Wilcoxon's sign rank test). This work further supports the safety and effectiveness of aDBS stimulation compared to cDBS in a daily session, both in terms of motor performance and TEED to the patient.
| S-EPMC8478873 | biostudies-literature