Deep Brain Stimulation Of The Subthalamic Nucleus Research Articles

Short term cardiovascular symptoms improvement after deep brain stimulation in patients with Parkinson's disease: a systematic review.

Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly understood. We aimed to assess the effect of DBS on cardiovascular symptoms and objective measures in PD patients. We conducted a systematic literature search in PubMed/MEDLINE. 36 out of 472 studies were included, mostly involving DBS of the subthalamic nucleus, and to a lesser extent the globus pallidus pars interna and pedunculopontine nucleus. Seventeen studies evaluated the effect of DBS on patient-reported or clinician-rated cardiovascular symptoms, showing an improvement in the first year after surgery but not with longer-term follow-up. DBS has no clear direct effects on blood pressure during an orthostatic challenge (n = 10 studies). DBS has inconsistent effects on heart rate variability (n = 10 studies). Current evidence on the impact of DBS on cardiovascular functions in PD is inconclusive. DBS may offer short-term improvement of cardiovascular symptoms in PD, particularly orthostatic hypotension, which may be attributed to dopaminergic medication reduction after surgery. There is insufficient evidence to draw conclusions on the direct effect of DBS on blood pressure and heart rate variability.

Kinematic Effects of Combined Subthalamic and Dorsolateral Nigral Deep Brain Stimulation in Parkinson's Disease.

Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson's disease (PD). This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulation sites within the SNr. In a double-blinded crossover design, 10 patients with PD and gait impairment underwent clinical examination and kinematic assessment with STN DBS, combined STN+SNr DBS and OFF DBS 30 minutes after reprogramming. To confirm stimulation within the SNr, electrodes, active contacts, and stimulation volumes were modeled in a common space and overlap with atlases of SNr was computed. Overlap of stimulation volumes with dorsolateral SNr was confirmed for all patients. UPDRS III, scoring of freezing during turning and transitioning, stride length, stride velocity, and range of motion of shank, knee, arm, and trunk as well as peak velocities during turning and transitions and turn duration were improved with STN DBS compared to OFF. On cohort level, no further improvement was observed with combined STN+SNr DBS but additive improvement of spatiotemporal gait parameters was observed in individual subjects. Combined high frequency DBS of the STN and dorsolateral SNr did not consistently result in additional short-term kinematic or clinical benefit compared to STN DBS. Stimulation intervals, frequency, and patient selection for target symptoms as well as target region within the SNr need further refinement in future trials.

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson’s disease

Background and objectivesThe intricate relationship between deep brain stimulation (DBS) in Parkinson’s disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. MethodsPre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population – Dementia Rating Scale 2. ResultsPD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. ConclusionsOur findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

Nanoscale Magneto-mechanical-genetics of Deep Brain Neurons Reversing Motor Deficits in Parkinsonian Mice.

Here, we introduce the magneto-mechanical-genetic (MMG)-driven wireless deep brain stimulation (DBS) using magnetic nanostructures for therapeutic benefits in the mouse model of Parkinson's disease (PD). Electrical DBS of the subthalamic nucleus (STN) is an effective therapy for mitigating Parkinson's motor symptoms. However, its broader application is hampered by the requirement for implanted electrodes and the lack of anatomical and cellular specificity. Using the nanoscale magnetic force actuators (m-Torquer), which deliver torque force under rotating magnetic fields to activate pre-encoded Piezo1 ion channels on target neurons, our system enables wireless and STN-specific DBS without implants, addressing key unmet challenges in the DBS field. In both late- and early-stage PD mice, MMG-DBS significantly improved locomotor activity and motor balance by 2-fold compared to untreated PD mice. Moreover, MMG-DBS enabled sustained therapeutic effects. This approach provides a non-invasive and implant-free DBS with cellular targeting capability for the effective treatment of Parkinsonian symptoms.

Anatomical targeting for electrode localization in subthalamic nucleus deep brain stimulation: A comparative study.

In deep brain stimulation (DBS), accurate electrode placement is essential for optimizing patient outcomes. Localizing electrodes enables insight into therapeutic outcomes and development of metrics for use in clinical trials. Methods of defining anatomical targets have been described with varying accuracy and objectivity. To assess variability in anatomical targeting, we compare four methods of defining an appropriate target for DBS of the subthalamic nucleus for Parkinson's disease. The methods compared are direct visualization, red nucleus-based indirect targeting, mid-commissural point-based indirect targeting, and automated template-based targeting. This study assessed 226 hemispheres in 113 DBS recipients (39 females, 73 males, 62.2±7.7years). We utilized the electrode placement error (the Euclidean distance between the defined target and closest DBS electrode) as a metric for comparative analysis. Pairwise differences in electrode placement error across the four methods were compared using the Kruskal-Wallis H-test and Wilcoxon signed-rank tests. Interquartile ranges of the differences in electrode placement error spanned 1.18-1.56mm. A Kruskal-Wallis H-test reported a statistically significant difference in the median of at least two groups (H(5) = 41.052, p<.001). Wilcoxon signed-rank tests reported statistically significant difference in two comparisons: direct visualization versus red nucleus-based indirect, and direct visualization versus automated template-based methods (T<9215, p<.001). All methods were similarly discordant in their relative accuracy, despite having significant technical differences in their application. The differing protocols and technical aspects of each method, however, have the implication that one may be more practical depending on the clinical or research application at hand.

The effect of deep brain stimulation in Parkinson’s disease reflected in EEG microstates

Mechanisms of deep brain stimulation (DBS) on cortical networks were explored mainly by fMRI. Advanced analysis of high-density EEG is a source of additional information and may provide clinically useful biomarkers. The presented study evaluates EEG microstates in Parkinson’s disease and the effect of DBS of the subthalamic nucleus (STN). The association between revealed spatiotemporal dynamics of brain networks and changes in oscillatory activity and clinical examination were assessed. Thirty-seven patients with Parkinson’s disease treated by STN-DBS underwent two sessions (OFF and ON stimulation conditions) of resting-state EEG. EEG microstates were analyzed in patient recordings and in a matched healthy control dataset. Microstate parameters were then compared across groups and were correlated with clinical and neuropsychological scores. Of the five revealed microstates, two differed between Parkinson’s disease patients and healthy controls. Another microstate differed between ON and OFF stimulation conditions in the patient group and restored parameters in the ON stimulation state toward to healthy values. The mean beta power of that microstate was the highest in patients during the OFF stimulation condition and the lowest in healthy controls; sources were localized mainly in the supplementary motor area. Changes in microstate parameters correlated with UPDRS and neuropsychological scores. Disease specific alterations in the spatiotemporal dynamics of large-scale brain networks can be described by EEG microstates. The approach can reveal changes reflecting the effect of DBS on PD motor symptoms as well as changes probably related to non-motor symptoms not influenced by DBS.

Lead-DBS v3.0: Mapping deep brain stimulation effects to local anatomy and global networks

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expanding clinical indications for DBS, increasing availability of related research tools, and a growing community of clinician-scientist researchers, however, have led to an ongoing need to maintain, update, and standardize the codebase of Lead-DBS. Major development efforts of the platform in recent years have now yielded an end-to-end solution for DBS-based neuroimaging analysis allowing comprehensive image preprocessing, lead localization, stimulation volume modeling, and statistical analysis within a single tool. The aim of the present manuscript is to introduce fundamental additions to the Lead-DBS pipeline including a deformation warpfield editor and novel algorithms for electrode localization. Furthermore, we introduce a total of three comprehensive tools to map DBS effects to local, tract- and brain network-levels. These updates are demonstrated using a single patient example (for subject-level analysis), as well as a retrospective cohort of 51 Parkinson's disease patients who underwent DBS of the subthalamic nucleus (for group-level analysis). Their applicability is further demonstrated by comparing the various methodological choices and the amount of explained variance in clinical outcomes across analysis streams. Finally, based on an increasing need to standardize folder and file naming specifications across research groups in neuroscience, we introduce the brain imaging data structure (BIDS) derivative standard for Lead-DBS. Thus, this multi-institutional collaborative effort represents an important stage in the evolution of a comprehensive, open-source pipeline for DBS imaging and connectomics.

Implementing automation in deep brain stimulation: has the time come?

In The Lancet Digital Health, Jan Roediger and colleagues1 present the results of a prospective, randomised, double-blind, crossover clinical trial assessing the therapeutic benefit of deep brain stimulation (DBS) settings derived from individual neuroimaging metrics. This evaluates a data-driven model of automated DBS parameter setting, maximising the predicted motor symptom control while accounting for potential stimulation-induced side-effects. Compared with current standard of care, the longer monopolar review based on existing clinical algorithms, the authors established non-inferiority of motor symptom control in a cohort of 35 patients with Parkinson's disease treated with DBS of the subthalamic nucleus.

Risk Factors for Hiccups after Deep Brain Stimulation of Subthalamic Nucleus for Parkinson's Disease.

After deep brain stimulation (DBS), hiccups as a complication may lead to extreme fatigue, sleep deprivation, or affected prognosis. Currently, the causes and risk factors of postoperative hiccups are unclear. In this study, we investigated the risk factors for hiccups after DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD) under general anesthesia. We retrospectively included patients who underwent STN DBS in the study, and collected data of demographic characteristics, clinical evaluations, and medications. According to the occurrence of hiccups within seven days after operation, the patients were divided into a hiccups group and non-hiccups group. The potentially involved risk factors for postoperative hiccups were statistically analyzed by logistic regression analysis. A total of 191 patients were included in the study, of which 34 (17.80%) had postoperative transient persistent hiccups. Binary univariate logistic regression analysis showed that male, higher body mass index (BMI), smoker, Hoehn and Yahr stage (off), preoperative use of amantadine, hypnotic, Hamilton anxiety scale and Hamilton depression scale scores, and postoperative limited noninfectious peri-electrode edema in deep white matter were suspected risk factors for postoperative hiccups (p &lt; 0.1). In binary multivariate logistic regression analysis, male (compared to female, OR 14.00; 95% CI, 1.74-112.43), postoperative limited noninfectious peri-electrode edema in deep white matter (OR, 7.63; 95% CI, 1.37-42.37), preoperative use of amantadine (OR, 3.64; 95% CI, 1.08-12.28), and higher BMI (OR, 3.50; 95% CI, 1.46-8.36) were independent risk factors for postoperative hiccups. This study is the first report about the risk factors of hiccups after STN DBS under general anesthesia for PD patients. The study suggests that male, higher BMI, preoperative use of amantadine, and postoperative limited noninfectious peri-electrode edema in deep white matter are independent risk factors for postoperative hiccups of STN-DBS for PD patients. Most hiccups after STN-DBS for PD patients were transient and self-limiting.

Post-mortem brain histological examination in the substantia nigra and subthalamic nucleus in Parkinson's disease following deep brain stimulation.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, pathologically hallmarked by the loss of dopamine neurons in the substantia nigra (SN) and alpha-synuclein aggregation. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common target to treat the motor symptoms in PD. However, we have less understanding of the cellular changes in the STN during PD, and the impact of DBS on the STN and SN is limited. We examined cellular changes in the SN and STN in PD patients with and without STN-DBS treatment. Post-mortem brain tissues from 6 PD non-STN-DBS patients, 5 PD STN-DBS patients, and 6 age-matched controls were stained with markers for neurodegeneration (tyrosine hydroxylase, alpha-synuclein, and neuronal loss) and astrogliosis (glial fibrillary acidic protein). Changes were assessed using quantitative and semi-quantitative microscopy techniques. As expected, significant neuronal cell loss, alpha-synuclein pathology, and variable astrogliosis were observed in the SN in PD. No neuronal cell loss or astrogliosis was observed in the STN, although alpha-synuclein deposition was present in the STN in all PD cases. DBS did not alter neuronal loss, astrogliosis, or alpha-synuclein pathology in either the SN or STN. This study reports selective pathology in the STN with deposits of alpha-synuclein in the absence of significant neuronal cell loss or inflammation in PD. Despite being effective for the treatment of PD, this small post-mortem study suggests that DBS of the STN does not appear to modulate histological changes in astrogliosis or neuronal survival, suggesting that the therapeutic effects of DBS mechanism may transiently affect STN neural activity.

Deep Brain Stimulation and Microelectrode Recording for the Treatment of Parkinson’s Disease

Parkinson’s disease (PD) is a neurological disorder in which nigrostriatal pathways involving the basal ganglia experience a decrease in neural activity regarding dopaminergic neurons. PD symptoms, such as muscle stiffness and involuntary tremors, have an adverse impact on the daily lives of those affected. Current medical treatments seek to decrease the severity of these symptoms. Deep brain stimulation (DBS) has become the preferred safe, and reliable treatment approach. DBS involves implanting microelectrodes into subcortical areas that produce electrical impulses directly to high populations of dopaminergic neurons. The most common targets are the subthalamic nucleus (STN), and the basal ganglia's globus pallidus pars interna (GPi). Research studies suggest that DBS of the STN may cause a significant reduction in the daily dose of L-DOPA compared to DBS of the GPi. DBS of the STN has suggested that there may be sweet spots within the STN that provide hyper-direct cortical connectivity pathways to the primary motor cortex (M1), supplementary motor area (SMA), and prefrontal cortex (PFC). In addition, the pedunculopontine nucleus (PPN) may be a new target for DBS that helps treat locomotion problems associated with gait and posture. Both microelectrode recording (MER) and magnetic resonance imaging (MRI) are used to ensure electrode placement accuracy. Using MER, stimulation of the STN at high frequencies (140<) decreased oscillatory neuronal firing by 67%. This paper investigates methods of intraoperative neuromonitoring during DBS as a form of PD treatment.

Subthalamic nucleus deep brain stimulation programming settings do not correlate with Parkinson's disease severity.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD). While the success of DBS is dependent on careful patient selection and accurate lead placement, programming parameters play a pivotal role in tailoring therapy on the individual level. Various algorithms have been developed to streamline the initial programming process, but the relationship between pre-operative patient characteristics and post-operative device settings is unclear. In this study, we investigated how PD severity correlates with DBS settings. We conducted a retrospective review of PD patients who underwent DBS of the subthalamic nucleus at one US tertiary care center between 2014 and 2018. Pre-operative patient characteristics and post-operative programming data at various intervals were collected. Disease severity was measured using the Unified Parkinson's Disease Rating Scale score (UPDRS) as well as levodopa equivalent dose (LED). Correlation analyses were conducted looking for associations between pre-operative disease severity and post-operative programming parameters. Fifty-six patients were analyzed. There was no correlation between disease severity and any of the corresponding programming parameters. Pre-operative UPDRS scores on medication were similar to post-operative scores with DBS. Settings of amplitude, frequency, and pulse width increased significantly from 1 to 6months post-operatively. Stimulation volume, inferred by the distance between contacts used, also increased significantly over time. Interestingly, we found that patients with more advanced disease responded to electrical stimulation similarly to patients with less advanced disease. These data provide foundational knowledge of DBS programming parameters used in a single cohort of PD patients over time.

Personality Related to Quality-of-Life Improvement After Deep Brain Stimulation in Parkinson's Disease (PSYCHO-STIM II).

Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson's disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients' quality of life (QoL) amelioration after DBS-STN. We hypothesized that personality dimensions might affect QoL after DBS-STN. To evaluate associations between personality dimensions and QoL improvement one year after DBS-STN. DBS-STN-PD patients (n = 303) having answered the "Temperament and Character Inventory" (TCI) before surgery and the PDQ-39 before and one year after surgery were included, from the cohort study PREDI-STIM. Linear regression models were used to evaluate associations between TCI dimensions and change in PDQ-39 scores after DBS-STN. Novelty Seeking and Cooperativeness scores before surgery were positively associated with PDQ-39 scores improvement after DBS-STN (FDR-adjusted p < 0.01). Moreover, paradoxically unimproved patients with deterioration of their PDQ-39 scores after DBS-STN despite improvement of their MDS-UPDRS-IV scores had lower Cooperativeness scores, while paradoxically improved patients with amelioration of their PDQ-39 scores despite deterioration of their MDS-UPDRS-IV scores had higher Reward Dependence scores. Some presurgical personality dimensions were significantly associated with QoL amelioration and discrepancy between motor state and QoL changes after DBS-STN in PD. Educational programs before DBS-STN should take in account patient personality dimensions to better deal with their expectations.

Impact of HIV impact on outcomes of deep-brain stimulation of the subthalamic nucleus for Parkinson's disease.

Middle-aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age-related comorbidities that are acknowledged as signs of poorer prognosis after deep-brain stimulation of the subthalamic nucleus (STN-DBS) at younger-than-expected ages. To assess the beneficial and adverse effects of STN-DBS in PLHIV with Parkinson's disease (PD). We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7±4years. Patients' mean ages at PD onset and STN-DBS were 45±15 and 53±16years, respectively. At STN-DBS, mean HIV infection and PD durations were 15±12 and 8±4years, respectively. STN-DBS significantly improved 1-year Unified Parkinson's Disease Rating Scale (UPDRS)-III scores (71%), daily off-time (63%), motor fluctuations (75%) and daily levodopa-equivalent dose (68%); mean 5-year UPDRS-III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN-DBS. Postoperative course was uneventful. No serious adverse events occurred during follow-up. Our findings indicate that STN-DBS is a safe and effective treatment for PLHIV with PD.

“Accidental, really?” Attributional bias in patients with Parkinson's disease

IntroductionAmong the cognitive domains impaired in Parkinson's disease (PD), social cognition has received particular attention in recent years. Nevertheless, attributional bias, a social-cognitive subdomain, has not yet been studied in this population, despite its potential relationship with neuropsychiatric symptoms, and despite the possibility that deep-brain stimulation of the subthalamic nucleus, an effective treatment for disabling motor symptoms, worsens cognitive impairment. The present study therefore compared the attributional bias of patients with PD (stimulated and nonstimulated subgroups) with that of controls. It also explored the potential correlations between patients' attributional bias and their clinical scores. MethodsThirty-two patients with PD (12 stimulated and 20 nonstimulated) were recruited and matched with 32 healthy controls. Attributional bias was assessed using the Ambiguous Intentions Hostility Questionnaire, which yields three subscores: Hostility Bias, Aggression Bias, and Blame. Depressive symptoms (Hamilton Rating Scale for Depression), paranoid thoughts (Paranoia Scale), global cognition (Montreal Cognitive Assessment), and social functioning (Social Functioning Questionnaire) were also assessed. ResultsPatients exhibited more hostile and aggressive biases than controls, especially in ambiguous situations. Stimulated patients had greater hostility and aggression biases and a higher blame score than controls in accidental situations. No significant differences were observed between stimulated and nonstimulated patients. ConclusionTo our knowledge, this is the first study to have assessed attributional bias in patients with PD and explored the impact of deep-brain stimulation on this particular subdomain of social cognition. Results suggest that patients exhibit attributional bias, and this impairment may be exacerbated in stimulated patients.

Deep brain stimulation for movement disorder treatment: exploring frequency-dependent efficacy in a computational network model

A large-scale computational model of the basal ganglia network and thalamus is proposed to describe movement disorders and treatment effects of deep brain stimulation (DBS). The model of this complex network considers three areas of the basal ganglia region: the subthalamic nucleus (STN) as target area of DBS, the globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus. Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities are derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities (synchronisation index, mean synaptic activity and response efficacy) switch from normal to Parkinsonian conditions. Simulating DBS of the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and Parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.

P.042 Dopamine Dysregulation Syndrome in Parkinson’s Disease and its Management with Advanced Therapies

Background: Dopamine Dysregulation Syndrome (DDS) is an adverse non-motor complication of dopamine replacement therapy in Parkinson’s Disease. The current literature on DDS is limited, and it remains underdiagnosed and challenging to manage. Methods: We performed a retrospective chart review and classified patients according to risk factors that have been identified in the literature, UPDRS scores, intervention and outcome. Univariate analyses were performed to quantify these characteristics. Results: Prior psychiatric illness was identified in 70% of patients, impulse control disorder in 89% and substance abuse in 3.7%. Interventions included reduction of dopamine therapy (88.9%), deep brain stimulation (DBS) of the subthalamic nucleus (STN, 48.1%) or globus pallidus interna (GPi, 7.4%), and levodopa-carbidopa intestinal gel (LCIG) infusion (11.1%). Baseline UPDRS IV before treatment and MDS III after treatment were not significant between intervention groups (p=0.09 and p=0.13 respectively). Overall 88.9% patients improved at follow up, with medication only (75%), STN DBS (100%), GPi DBS (100%) and LCIG (33%). Relapse rate was 18.2%, in the STN group only. Conclusions: Our results suggest that GPi DBS, in concurrence with dopaminergic medication reduction, is the most effective intervention. STN DBS might be also beneficial although the associated medications reduction causes DDS relapse in a subgroup of patients.

Effect of bilateral deep brain stimulation on the subthalamic nucleus on patients with Parkinson's disease: An observational and non-blinded study

ObjectiveThis study analyzed the influence of subthalamic nucleus deep brain stimulation (DBS) in motor parameters and patients' quality of life with Parkinson's disease (PD) evaluated before and after 12 months of the surgical procedure. MethodsA cohort of 20 patients with PD who underwent DBS implantation in the subthalamic nucleus was included. Pre and on-DBS postoperative data in on and off-medication periods related to motor functions and quality of life, from the application of validated scales, were collected to verify possible relationships between changes in these parameters and the surgical procedure. ResultsA significant decrease in the Hoehn and Yahr scale disease stage and in the levodopa equivalent dose (p < 0.001) was verified in the off-medication period when we compared baseline and post-12 months data. A significant decrease in dyskinesias (p = 0.009) was observed during the on-medication period by evaluating the UDysRS scale. Concerning motor functions verified through the UPDRS-III scale, it was obtained a significant reduction in total scores (p = 0.001), besides a decrease in rigidity scores for upper and lower limbs (p < 0.05) during the on-medication period. During the off-medication period, scores of UPDRS-III demonstrated a significant decrease, except for the ones related to speech and amplitude of resting tremor. Regarding the quality-of-life assessment, scores obtained from PDQ-39 showed that, after 12 months of electrode implantation, there was a significant decrease in mobility, daily living activity, and stigma parameters (p < 0.05). ConclusionsResults obtained allow us to conclude that DBS of the subthalamic nucleus in patients with PD improves motor function in both on and off-medication periods, improvement of the disease stage in the off-medication period, with no change in the on-medication period, also an improvement in the patient's self-reported quality of life and a significant reduction in the dose of L-DOPA.

The software defined implantable modular platform (STELLA) for preclinical deep brain stimulation research in rodents

Context. Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals’ behavior. Objective. To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models. Approach. We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6 µA/3.1 V combined with an epoxy resin-based encapsulation method. Main results. STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. While in vitro studies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA. Significance. We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to ‘The Principle of Humane Experimental Technique’—replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.

Gamma Oscillations and Coherence Are Weaker in the Dorsomedial Subregion of STN in Parkinson's Disease.

Background: Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor symptoms of advanced Parkinson's disease (PD). Due to a lack of detailed somatotopic organization in STN, the clinically most effective part of the STN for stimulation has already become one of the hot research focuses. At present, there are some reports about topographic distribution for different depths within the STN, but few about a mediolateral topography in this area.Objective: The objective was to investigate the local field potential (LFP) distribution patterns in dorsomedial and dorsolateral subparts of STN.Methods: In total, 18 PD patients eventually enrolled in this study. The DBS electrodes were initially located on the lateral portion of dorsolateral STN. Because of internal capsule side effects presented at low threshold (below 1.5 mA), the electrode was reimplanted more medially to the dorsomedial STN. In this process, intraoperative LFPs from dorsomedial and dorsolateral STN were recorded from the inserted electrode. Both beta power and gamma power of the LFPs were calculated using the power spectral density (PSD) for each DBS contact pair. Furthermore, coherence between any two pairs of contacts was computed in the dorsomedial and dorsolateral parts of STN, respectively. Meanwhile, the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) was monitored prior to surgery and at the 6-month follow-up.Results: Compared to the dorsolateral part of STN, gamma oscillations (p < 0.01) and coherence (p < 0.05) were all weaker in the dorsomedial part. However, no obvious differences in beta oscillations and coherence were observed between the two groups (p > 0.05). Moreover, it should be noted that DBS of the dorsomedial STN resulted in significant improvement in the UPDRS-III in PD patients. There was a 61.50 ± 21.30% improvement in UPDRS-III scores in Med-off/Stim-on state relative to the Med-off state at baseline (from 15.44 ± 6.84 to 43.94 ± 15.79, p < 0.01).Conclusions: The specific features of gamma activity may be used to differentiate STN subregions. Moreover, the dorsomedial part of STN might be a potential target for DBS in PD.