Deep Brain Stimulation at Variable Frequency to Improve Motor Outcomes in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Jia F
PROVIDER: S-EPMC6207106 | biostudies-literature | 2018 Sep-Oct
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Contemporary deep brain stimulation (DBS) for Parkinson's disease is delivered continuously, and adjustments based on patient's changing symptoms must be made manually by a trained clinician. Patients may be subjected to energy intensive settings at times when they are not needed, possibly resulting in stimulation-induced adverse effects, such as dyskinesia. One solution is 'adaptive' DBS, in which stimulation is modified in real time based on neural signals that co-vary with the severity of motor signs or of stimulation-induced adverse effects. Here we show the feasibility of adaptive DBS using a fully implanted neural prosthesis. APPROACH:We demonstrate adaptive deep brain stimulation in two patients with Parkinson's disease using a fully implanted neural prosthesis that is enabled to utilize brain sensing to control stimulation amplitude (Activa PC??+??S). We used a cortical narrowband gamma (60-90 Hz) oscillation related to dyskinesia to decrease stimulation voltage when gamma oscillatory activity is high (indicating dyskinesia) and increase stimulation voltage when it is low. MAIN RESULTS:We demonstrate the feasibility of 'adaptive deep brain stimulation' in two patients with Parkinson's disease. In short term in-clinic testing, energy savings were substantial (38%-45%), and therapeutic efficacy was maintained. SIGNIFICANCE:This is the first demonstration of adaptive DBS in Parkinson's disease using a fully implanted device and neural sensing. Our approach is distinct from other strategies utilizing basal ganglia signals for feedback control.
| S-EPMC6021210 | biostudies-literature
Project description:The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson's disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-frequency interactions with gamma oscillations in a cortico-subcortical network of interconnected regions and normalizes the balance between beta and gamma oscillations. To this end we acquired resting state high-density (256 channels) EEG from 31 patients with Parkinson's disease who underwent deep brain stimulation to compare spectral power and power-to-power cross-frequency coupling using a beamformer algorithm for coherent sources. To show that modulations exclusively relate to stimulation frequencies that alleviate motor symptoms, two clinically ineffective frequencies were tested as control conditions. We observed a robust reduction of beta and increase of gamma power, attested in the regions of a cortical (motor cortex, supplementary motor area, premotor cortex) and subcortical network (subthalamic nucleus and cerebellum). Additionally, we found a clear cross-frequency coupling of narrowband gamma frequencies to the stimulation frequency in all of these nodes, which negatively correlated with motor impairment. No such dynamics were revealed within the control posterior parietal cortex region. Furthermore, deep brain stimulation at clinically ineffective frequencies did not alter the source power spectra or cross-frequency coupling in any region. These findings demonstrate that clinically effective deep brain stimulation of the subthalamic nucleus differentially modifies different oscillatory activities in a widespread network of cortical and subcortical regions. Particularly the cross-frequency interactions between finely tuned gamma oscillations and the stimulation frequency may suggest an entrainment mechanism that could promote dynamic neural processing underlying motor symptom alleviation.
| S-EPMC7116448 | biostudies-literature
Project description:ObjectivesTo evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome.MethodsWe retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point.ResultsAt 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease.ConclusionsSTN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted.
| S-EPMC6043715 | biostudies-literature
Project description:BackgroundThe up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson's disease (PD) is lacking.ObjectiveTo address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS.MethodsWe used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted.ResultsThe STN-DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS-III at both 6- and 12-month follow-ups (P < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow-up times. For the sub-scores of UPDRS-III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor (P = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS-III total score at a median follow-up of 12 months (P = 0.030).ConclusionThe current study confirmed the value of preoperative levodopa responsiveness for prediction of the short-term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short-term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long-term motor outcomes were highlighted by this study.
| S-EPMC8810442 | biostudies-literature
Project description:Objective: Deep brain stimulation of the Subthalamic nucleus (STN-DBS) is a safe and well-established therapy for the management of refractory motor symptoms in Parkinson's disease (PD). Marked improvement in axial symptoms has been reported in the short term with STN-DBS but questions remain regarding the long-term efficacy of this intervention. We assessed the acute ON and OFF effects of STN-DBS in PD patients who have been treated with STN-DBS for over a decade. Methods: We assessed 11 patients with early-onset PD (9 men, 2 women; mean age, 57.1 ± 7.2 y; mean age at illness onset, 38.9 ± 7.5 y) managed with long-term bilateral STN-DBS (mean treatment duration, 13.4 ± 1.3 y). Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS)-III, Timed Up and Go test (TUG), and Hoehn-Yahr scale. Motor assessments in the medication ON and OFF states with stimulation ON and OFF conditions were documented and video recorded. Results: Patients showed a significant improvement in motor symptoms both in the off-medication and on-medication state by a 54% reduction (off-medication/on-stimulation vs. off-medication/off-stimulation) and a 48% reduction (on-medication/on-stimulation vs. on-medication/off-stimulation) in the total UPDRS-III score. Specifically, improvement in axial symptoms (off-medication: 51% reduction; on-medication: 44% reduction), including gait but not posture. Similarly, STN-DBS reduced TUG scores (off-medication: 70% reduction; on-medication: 47% reduction). Conclusions: On stimulation long-term, bilateral STN-DBS can improve appendicular and axial symptoms of patients with early-onset PD in the acute setting.
| S-EPMC6606731 | biostudies-literature
Project description:BackgroundDeep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson's disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial.Methods/designWe propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand-walk-sit task scores after 3 months of treatment in the "medication off" condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation.DiscussionThis is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future.Trial registrationClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.
| S-EPMC6924017 | biostudies-literature
Project description:ObjectiveThe aim of this study was to evaluate the neurobehavioral safety of constant-current subthalamic deep brain stimulation and to compare the neuropsychological effects of stimulation versus electrode placement alone.MethodsA total of 136 patients with Parkinson's disease underwent bilateral subthalamic device implantation in this randomized trial. Patients received stimulation either immediately after device implantation (n = 101; active stimulation) or beginning 3 months after surgery (n = 35; delayed activation control). Patients were administered neuropsychological tests before, 3, and 12 months after device implantation.ResultsNeuropsychological change in stimulation and control groups were comparable. Within-group analyses revealed declines in category and switching verbal fluency in both groups, but only the stimulation group had letter verbal fluency and Stroop task declines. Depression symptom improvements occurred in both groups, but more often in the stimulation group. Letter fluency declines were associated with worse Parkinson's Disease Questionnaire Communication subscale scores. Baseline and 12-month comparisons (in the combined group) revealed gains in verbal and visual delayed recall scores and improvement in depression symptoms, but decrements in verbal fluency and Stroop scores.ConclusionsConstant-current bilateral subthalamic stimulation had a good cognitive safety profile except for decrements in verbal fluency and on the Stroop task. These abnormalities are related to device implantation, but stimulation likely had an additive effect. One year after surgery, the cognitive changes did not exert a detrimental effect on quality of life, although letter fluency declines were associated with communication dissatisfaction at 12 months. Improvement in depressive symptom severity appears dependent on stimulation and not placebo or lesion effects. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC5363377 | biostudies-literature
Project description:Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson's disease (PD). Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively. Results: Pearson's correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R 2 = 0.283, p = 0.016) but not on the non-tremor total score (R 2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R 2' = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R 2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R 2 = 0.290, p = 0.021), but not on the total score (R 2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R 2' = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor. Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.
| S-EPMC7889513 | biostudies-literature
Project description:ObjectiveDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson's disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects.MethodsIn the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level-dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation.ResultsAs expected, DBS resulted in blood oxygen level-dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson's Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen).ConclusionsThese results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.
| S-EPMC10193504 | biostudies-literature
Project description:Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500 Hz) oscillation that typically has a duration of at least 10 ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130 Hz stimulation at increasing amplitudes (0.67-3.38 mA), 'washout' of therapeutic effects, and non-therapeutic 20 Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130 Hz stimulation (p < .001). This modulation coincided with improvement in bradykinesia and rigidity (p < .001), and correlated with spontaneous beta band suppression (p < .001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400 Hz), both of which decreased to around twice the 130 Hz stimulation rate. Non-therapeutic stimulation at 20 Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.
| S-EPMC6879321 | biostudies-literature