Modulation of subthalamic beta oscillations by movement, dopamine, and deep brain stimulation in Parkinson's disease.

Subthalamic beta band activity (13-35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson's disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activity in PD patients implanted with sensing-enabled, implantable pulse generators. We recorded subthalamic activity from seven PD patients at rest and during repetitive movements in four conditions: after withdrawal of dopaminergic medication and DBS, with medication only, with DBS only, and with simultaneous medication and DBS. Medication and DBS showed additive effects in improving motor performance. Distinct effects of each therapy were seen in subthalamic recordings, with medication primarily suppressing low beta activity (13-20 Hz) and DBS being associated with a broad decrease in beta band activity (13-35 Hz). Movement suppressed beta band activity compared to rest. This suppression was most prominent when combining medication with DBS and correlated with motor improvement within patients. We conclude that DBS and medication have distinct effects on subthalamic beta activity during both rest and movement, which might explain their additive clinical effects as well as their difference in side-effect profiles. Importantly, subthalamic beta activity significantly correlated with motor symptoms across all conditions, highlighting its validity as a feedback signal for closed-loop DBS.

Effect of implant type on the stability of cantilever fixed dental prostheses: An in vitro study.

OBJECTIVES: To simulate the replacement of a premolar with an implant-supported cantilever fixed dental prosthesis (ICFDP) and how the fracture load is affected by implant type, positioning within the zirconia blank, and aging protocol. MATERIALS AND METHODS: Seventy-two ICFDPs were designed either within the enamel- or dentin layer of a 4Y-PSZ blank for bone-level and tissue-level titanium-zirconium implants. Fracture load was obtained on the cantilever at baseline (no aging) or after aging in a chewing simulator with the load applied within the implant axis (axial aging) or on the cantilever (12 groups with n = 6). A three-way ANOVA was applied (α = .05). RESULTS: A three-way ANOVA revealed a significant effect on fracture load values of implant type (p = .006) and aging (p < .001) but not for the position within the zirconia blank (p = .847). Fracture load values significantly increased from baseline bone level (608 ± 118 N) and tissue level (880 ± 293 N) when the implants were aged axially, with higher values for tissue level (1065 ± 182 N) than bone level (797 ± 113 N) (p < .001). However, when the force was applied to the cantilever, fracture load values decreased significantly for tissue-level (493 ± 70 N), while values for bone-level implants remained stable (690 ± 135 N). CONCLUSIONS: For ICFDPs, the use of bone-level implants is reasonable as catastrophic failures are likely to be restricted to the restoration, whereas with tissue-level implants, the transmucosal portion of the implant is susceptible to deformation, making repair more difficult.

Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons.

BACKGROUND: Electrophysiological recording with glass electrodes is one of the best techniques to measure membrane potential dynamics and ionic currents of voltage-gated channels in neurons. However, artifactual variability of the biophysical state variables that determine recording quality can be caused by insufficient affinity between the electrode and cell membrane during the recording. NEW METHOD: We introduce a phospholipid membrane coating on glass electrodes to improve intracellular electrophysiology recording quality. Membrane-coated electrodes were prepared with a tip-dip protocol for perforated-patch, sharp-electrode current-clamp, and cell-attached patch-clamp recordings from specific circadian clock neurons in Drosophila. We perform quantitative comparisons based on the variability of functional biophysical parameters used in various electrophysiological methods, and advanced statistical comparisons based on the degree of stationariness and signal-to-noise ratio. RESULTS: Results indicate a dramatic reduction in artifactual variabilities of functional parameters from enhanced stability. We also identify significant exclusions of a statistically estimated noise component in a time series of membrane voltage signals, improving signal-to-noise ratio. COMPARISON WITH EXISTING METHODS: Compared to standard glass electrodes, using membrane-coated glass electrodes achieves improved recording quality in intracellular electrophysiology. CONCLUSIONS: Electrophysiological recordings from Drosophila central neurons can be technically challenging, however, membrane-coated electrodes will possibly be beneficial for reliable data acquisition and improving the technical feasibility of axonal intracellular activities measurements and single-channel recordings. The improved electrical stability of the recordings should also contribute to increased mechanical stability, thus facilitating long-term stable measurements of neural activity. Therefore, it is possible that membrane-coated electrodes will be useful for any model system.

Single threshold adaptive deep brain stimulation in Parkinson's disease depends on parameter selection, movement state and controllability of subthalamic beta activity.

BACKGROUND: Deep brain stimulation (DBS) is an invasive treatment option for patients with Parkinson's disease. Recently, adaptive DBS (aDBS) systems have been developed, which adjust stimulation timing and amplitude in real-time. However, it is unknown how changes in parameters, movement states and the controllability of subthalamic beta activity affect aDBS performance. OBJECTIVE: To characterize how parameter choice, movement state and controllability interactively affect the electrophysiological and behavioral response to single threshold aDBS. METHODS: We recorded subthalamic local field potentials in 12 patients with Parkinson's disease receiving single threshold aDBS in the acute post-operative state. We investigated changes in two aDBS parameters: the onset time and the smoothing of real-time beta power. Electrophysiological patterns and motor performance were assessed while patients were at rest and during a simple motor task. We further studied the impact of controllability on aDBS performance by comparing patients with and without beta power modulation during continuous stimulation. RESULTS: Our findings reveal that changes in the onset time control the extent of beta power suppression achievable with single threshold adaptive stimulation during rest. Behavioral data indicate that only specific parameter combinations yield a beneficial effect of single threshold aDBS. During movement, action induced beta power suppression reduces the responsivity of the closed loop algorithm. We further demonstrate that controllability of beta power is a prerequisite for effective parameter dependent modulation of subthalamic beta activity. CONCLUSION: Our results highlight the interaction between single threshold aDBS parameter selection, movement state and controllability in driving subthalamic beta activity and motor performance. By this means, we identify directions for the further development of closed-loop DBS algorithms.

The interventions to improve medication adherence in coronary heart disease patient: A systematic review.

Objective: The clinical outcome and quality of life of CHD patients are greatly influenced by medication adherence. Non-adherence of CHD patients to treatment results in sub-optimal clinical outcomes and increasing costs. This study aims to describe effectiveness of the intervention to improve the medication adherence in CHD patients. Methods: Systematic review methodology was used in this study. Scopus and PubMed were used to search the relevant article systematically. The outcome measured was medication adherence in coronary heart disease patients. Results: Final screening was 31 articles that met the inclusion criteria in this study of 788 articles. Selection processes the article used the PRISMA guideline. Most of the articles (15 articles) use interventions that utilize information technology (IT) as known with m-health in the form of text messages, website, and smartphone-based applications in increasing medication adherence in CHD patients. The non m-health interventions developed are in the form of self-efficacy programs, monitoring and education by health workers or care workers, pharmacy care by clinical pharmacists, and the use of drugs in the form of multi-capsules. The results of most intervention with m-health can improve the medication adherence in CHD patient effectively. Education and motivation program by professional health care and multi-capsules also increasing the medication adherence in the intervention control. There was a decrease of medication adherence in some articles with long time follow-up that can be attention for the professional health care to manage the patient adherent. Conclusion: The medication adherence in CHD patient can be improve by various program. Modification of m-health and non m-health intervention can be resolved to increase the communication, motivation, and knowledge about medication adherence in CHD patients.

Dexmedetomidine as a myocardial protector in pediatric heart surgery using cardiopulmonary bypass: a systematic review.

Background: In recent years, dexmedetomidine has been studied as a cardioprotective agent. However, studies on its application in pediatric heart surgery using cardiopulmonary bypass (CPB) remain limited. This systematic review aimed to provide information on the cardioprotective effect of dexmedetomidine in children undergoing heart surgery using CPB. Methods: The authors searched several databases (MEDLINE, Embase, Cochrane Library, etc.) to identify all trials comparing the levels of myocardial injury via biomarkers, including pediatric patients undergoing heart surgery using CPB who received dexmedetomidine versus placebo or other anesthetic agents. Literatures from non-primary studies were excluded. Two reviewers independently screened studies for eligibility and extracted data. The Cochrane Risk-of-Bias tool was implemented to evaluate any potential biases. Information from eligible studies was summarized and correspondingly reviewed based on any quantitative outcomes. Results: We identified six trials composed of 419 participants, three of which (n=241) showed significantly reduced interleukin-6 (IL-6) levels in the dexmedetomidine group, while one study (n=40) showed no IL-6 difference between groups. Cardiac troponin I (cTnI) and creatinine kinase-myocardial band (CK-MB), as myocardial injury biomarkers, were found to be lower in two trials (n=180). Despite several limitations hindering this review from pooling the data objectively, the majority of published studies indicated that dexmedetomidine is a seemingly efficacious agent protecting against cardiac injury during bypass. Conclusions: These studies suggest that dexmedetomidine has cardioprotective effects through the lowering of cardiac injury biomarkers while improving its clinical outcomes after heart surgery using bypass.

Exploring the staining potential of 1 GSK-3 inhibitors in bovine teeth: 2 a one-year laboratory investigation.

GSK-3 inhibitors, such as Tideglusib (TG) and CHIR-99021 (CHIR), show promise in stimulating reparative dentin formation. The aim of this study was to assess the discoloration potential of TG and CHIR in an established in vitro model. Enamel-dentin specimens made from bovine incisors were randomly allocated to five groups (n=15 each): group bovine blood (BB), group dimethyl sulfoxide (DMSO), group TG, group CHIR, and group mineral trioxide aggregate (MTA). Each specimen had a central cavity in which the respective material was applied and sealed with resin-based luting material. Color determination was conducted using a dental spectrophotometer at t0 (before filling), t1 (immediately after filling), t2 (after one week), t3 (after one month), t4 (after three months), t5 (after six months), and t6 (after one year). Statistical analysis involved descriptive statistics, Kruskal-Wallis tests, and analysis of variance (α=0.05). Group BB and group CHIR exhibited the most significant decrease in lightness (ΔL*) after one year (ΔL*-4.7 and ΔL* -5.7, respectively), whereas groups DMSO, TG, and MTA showed minimal changes (DMSO ΔL*: -0.3; TG ΔL*: 1.4; MTA ΔL*: -0.5). Group BB and CHIR exhibited the highest ΔE values (6.4Å}0.6 and 6.5Å}0.8, respectively). Unlike CHIR, TG did not result in discoloration exceeding the threshold of visual perception, defined by a ΔE value of 5.5, during the one-year observation period. This laboratory study therefore suggests that TG could be utilized for indirect or direct pulp capping without major discoloration concerns. However, additional research is required to corroborate these findings.

Increased serum activin A level in congenital heart disease-associated pulmonary artery hypertension: A comparative study from the COHARD-PH registry.

Activin A, a member of TGF-ß superfamily, has been implicated in the pathogenesis of pulmonary artery hypertension (PAH). PAH due to congenital heart disease (CHD-PAH) is a major problem in developing countries. Activin A may have a role in PAH development and progression among uncorrected CHD. In this comparative study, serum activin A level was significantly increased in subjects with uncorrected CHD without the presence of PH and were more significantly risen in CHD-PAH, as compared to control. The utilization of serum activin A measurement seems promising to identify uncorrected CHD patients with PAH development and progression.

Biofilm formation on metal alloys and coatings, zirconia, and hydroxyapatite as implant materials in vivo.

OBJECTIVES: Composition of implant material and its surface structure is decisive for oral biofilm accumulation. This study investigated biofilm formation on eight different materials. MATERIALS AND METHODS: Eighteen healthy subjects wore intraoral splints fitted with two sets of eight materials for 24 h: zirconia [ZrO2 ]; silver-gold-palladium [AgAuPd]; titanium zirconium [TiZr]; Pagalinor [PA]; hydroxyapatite [HA]; silver-platinum [AgPt]; titanium aluminum niobium [TAN]; titanium grade4 [TiGr4]. Total biomass was stained by safranin to assess plaque accumulation while conventional culturing (CFU) was conducted to investigate viable parts of the biofilm. Cell viability of human gingival fibroblasts (HGF-1) was assessed in vitro. Statistical evaluation was performed with linear mixed-effects models to compare materials (geometric mean ratios, 95% CI), with the level of significance set at ɑ = .05. RESULTS: Less biofilm mass and CFU were found on noble metal alloys (AgPt, AgAuPd, and PA). Compared to AgPt, PA had 2.7-times higher biofilm mass value, AgAuPd was 3.9-times, TiGr4 was 4.1-times, TiZr was 5.9-times, TAN was 7.7-times, HA was 7.8-times, and ZrO2 was 9.1-times higher (each p < .001). Similarly, CFU data were significantly lower on AgPt, AgAuPd had 4.1-times higher CFU values, PA was 8.9-times, TiGr4 was 11.2-times, HA was 12.5-times, TiZr was 13.3-times, TAN was 16.9-times, and ZrO2 was 18.5-times higher (each p < .001). HGF-1 viability varied between 47 ± 24.5% (HA) and 94.4 ± 24.6% (PA). CONCLUSION: Noble alloys are considered as beneficial materials for the transmucosal part of oral implants, as less biofilm mass, lower bacterial counts, and greater cell viability were detected than on titanium- or zirconia-based materials.

A First Methodological Development and Validation of ReTap: An Open-Source UPDRS Finger Tapping Assessment Tool Based on Accelerometer-Data.

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia.

Pallidal Beta Activity Is Linked to Stimulation-Induced Slowness in Dystonia.

BACKGROUND: Pallidal deep brain stimulation (DBS) effectively alleviates symptoms in dystonia patients, but may induce movement slowness as a side-effect. In Parkinson's disease, hypokinetic symptoms have been associated with increased beta oscillations (13-30 Hz). We hypothesize that this pattern is symptom-specific, thus accompanying DBS-induced slowness in dystonia. METHODS: In 6 dystonia patients, pallidal rest recordings with a sensing-enabled DBS device were performed and tapping speed was assessed using marker-less pose estimation over 5 time points following cessation of DBS. RESULTS: After cessation of pallidal stimulation, movement speed increased over time (P < 0.01). A linear mixed-effects model revealed that pallidal beta activity explained 77% of the variance in movement speed across patients (P = 0.01). CONCLUSIONS: The association between beta oscillations and slowness across disease entities provides further evidence for symptom-specific oscillatory patterns in the motor circuit. Our findings might help DBS therapy improvements, as DBS-devices able to adapt to beta oscillations are already commercially available. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Christmas-Related Reduction in Beta Activity in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. OBJECTIVE: The aim was to investigate Christmas-related influences on beta activity in PD. METHODS: Differences in Christmas Day to nonfestive daily averages in chronic biomarker recordings in 4 PD patients with a sensing-enabled STN DBS implant were retrospectively analyzed. Sweet-spot and whole-brain network connectomic analyses were performed. RESULTS: Beta activity was significantly reduced on Christmas Eve in all patients (4.00-9.00 p.m.: -12.30 ± 10.78%, P = 0.015). A sweet spot in the dorsolateral STN connected recording sites to motor, premotor, and supplementary motor cortices. CONCLUSIONS: We demonstrate that festive events can reduce beta biomarker activity. We conclude that circadian and holiday-related changes should be considered when tailoring adaptive DBS algorithms to patient demands. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Risk factors associated with postpartum depression in a high-risk maternity clinic: a cross-sectional study.

BACKGROUND: The aim of this study was to evaluate obstetric, epidemiological and social factors related to postpartum depression (PPD) and investigate possible risk factors related to this disorder, in puerperal women who had their childbirth and were referred to the High-Risk Outpatient Clinic. METHODS: A cross-sectional study from August-December/2019 was carried out. One hundred seventy-one puerperal women were analyzed by filling out an epidemiological questionnaire and the Edinburgh Postpartum Depression Scale (EPDS) Form. Scores ≥10 were considered positive. Research on risk factors for postpartum depression was carried out. RESULTS: 29.8% of mothers had a score related with PPD. Breastfeeding without complication is protective against PPD (P=0.002 and χ2=12.533). In contrast, not having a planned pregnancy (P=0.0175, χ2=5.717), having depression at any stage of life (P=0.013, χ2=6.237), depression during pregnancy (P≤0.0001, χ2=46.201) or having a family history of depression (P=0.001, χ2=10.527), are factors associated with the development of PPD. Moreover, just having depression during pregnancy was found to be a significant risk factor for the occurrence of PPD, increasing the risk of developing this pathology by 12 times (OR=12.891). CONCLUSIONS: Depression during pregnancy is an important risk factor for the development of PPD. This can easily be detected using the Edinburgh Postpartum Depression Scale and treated in a timely manner.

Improving naturalistic neuroscience with patient engagement strategies.

Introduction: The clinical implementation of chronic electrophysiology-driven adaptive deep brain stimulation (DBS) algorithms in movement disorders requires reliable representation of motor and non-motor symptoms in electrophysiological biomarkers, throughout normal life (naturalistic). To achieve this, there is the need for high-resolution and -quality chronic objective and subjective symptom monitoring in parallel to biomarker recordings. To realize these recordings, an active participation and engagement of the investigated patients is necessary. To date, there has been little research into patient engagement strategies for DBS patients or chronic electrophysiological recordings. Concepts and results: We here present our concept and the first results of a patient engagement strategy for a chronic DBS study. After discussing the current state of literature, we present objectives, methodology and consequences of the patient engagement regarding study design, data acquisition, and study infrastructure. Nine patients with Parkinson's disease and their caregivers participated in the meeting, and their input led to changes to our study design. Especially, the patient input helped us designing study-set-up meetings and support structures. Conclusion: We believe that patient engagement increases compliance and study motivation through scientific empowerment of patients. While considering patient opinion on sensors or questionnaire questions may lead to more precise and reliable data acquisition, there was also a high demand for study support and engagement structures. Hence, we recommend the implementation of patient engagement in planning of chronic studies with complex designs, long recording durations or high demand for individual active study participation.

Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using minimally invasive encephalodurosynangiosis in patients with moyamoya angiopathy.

Moyamoya angiopathy (MMA) can be treated using direct, indirect, or combined revascularization procedures. We perform combined revascularization using the STA-MCA bypass and minimally invasive encephalodurosynangiosis (MIS-EDS). Due to lack of systematic analyses to date it remains unclear whether and to which extent this limited EDS serves as a growth source for extracerebral blood vessels into the brain. The objective of the current study is to characterize the extent of angiographic filling of MIS-EDS and STA-MCA bypass development over time and to determine possible predictors of EDS development in adult MMA patients. Single-center retrospective analysis of 81 MMA patients (139 hemispheres) treated with a MIS-EDS and STA-MCA bypass was performed. Angiographic images and clinical/operative data were reviewed and scored. Uni-/ and multivariate Cox regression analyses identified preoperative predictors of good EDS vascularization. At 3-6 months after surgery EDS showed moderate and high angiographic filling in 40% and 5% of hemispheres, respectively. After 12 months moderate and high filling was found in 57% and 4% of hemispheres, respectively. STA-MCA bypass filling was moderate in 47% and high in 7% of hemispheres at 3-6 months and 45% moderate and 9% high after 12 months. High STA-MCA bypass filling on angiography was a negative predictor of EDS development. MIS-EDS is a simple technique and serves as a source of vessel growth into the brain. EDS development lags behind that of STA-MCA bypass and can be recommended as an additive revascularization source when combined with a direct bypass.

Diurnal modulation of subthalamic beta oscillatory power in Parkinson's disease patients during deep brain stimulation.

Beta-band activity in the subthalamic local field potential (LFP) is correlated with Parkinson's disease (PD) symptom severity and is the therapeutic target of deep brain stimulation (DBS). While beta fluctuations in PD patients are well characterized on shorter timescales, it is not known how beta activity evolves around the diurnal cycle, outside a clinical setting. Here, we obtained chronic recordings (34 ± 13 days) of subthalamic beta power in PD patients implanted with the Percept DBS device during high-frequency DBS and analysed their diurnal properties as well as sensitivity to artifacts. Time of day explained 41 ± 9% of the variance in beta power (p < 0.001 in all patients), with increased beta during the day and reduced beta at night. Certain movements affected LFP quality, which may have contributed to diurnal patterns in some patients. Future DBS algorithms may benefit from taking such diurnal and artifactual fluctuations in beta power into account.

Feasibility of screening for critical congenital heart disease using pulse oximetry in Indonesia.

BACKGROUND: Screening of critical congenital heart disease (CCHD) using pulse oximetry is a routine procedure in many countries, but not in Indonesia. This study aimed to evaluate the feasibility of implementing CCHD screening with pulse oximetry for newborns in Yogyakarta, Indonesia. METHODS: A cross-sectional study was conducted at four hospitals in Yogyakarta, Indonesia. Newborns aged 24-48 hours who met the inclusion criteria were screened on the right hand and left or right foot using a pulse oximeter. Positive results were indicated by: either (1) SpO2 level < 90% in one extremity, (2) SpO2 level of 90-94% in both right hand and either foot on three measurements conducted 1 hour apart, or (3) a saturation difference > 3% between the upper and lower extremity on three measurements conducted 1 hour apart. Positive findings were confirmed by echocardiography. RESULTS: Of 1452 newborns eligible for screening, 10 had positive results and were referred for echocardiographic evaluation. Of those, 8 (6 per 1000 live birth, 8/1452) had CCHD. Barriers found during screening processes were associated with hospital procedures, equipment, healthcare personnel, and condition of the newborn. CONCLUSION: Pulse oximetry screening might be feasible to be implemented within the routine newborn care setting for CCHD in Indonesia. In order to successfully implement pulse oximetry screening to identify CCHD in Indonesia, the barriers will need to be addressed.

Stability of Cantilever Fixed Dental Prostheses on Zirconia Implants.

BACKGROUND: The objective was to determine the optimal connector size and position within zirconia disks for implant-supported cantilever fixed dental prostheses (ICFDP). METHODS: Two-unit ICFDPs (n = 60) were designed for the premolar region with connector sizes of either 9 or 12 mm2 and positioned in the enamel or dentin layer of two different types of zirconia disks. The restorations were milled and cemented onto zirconia implants. After simulated chewing for 1.2 Mio cycles, the fracture load was measured and fractures were analyzed. RESULTS: No fractures of ICFDPs or along the implants were detected after simulated aging. The mean fracture load values were significantly higher for a connector size of 9 mm2 (951 N) compared with 12 mm2 (638 N). For the zirconia material with a higher biaxial flexural strength, the fracture load values were increased from 751 to 838 N, but more implant fractures occurred. The position within the zirconia disk did not influence the fracture load. CONCLUSIONS: A connector size of 9 mm2 and a zirconia material with a lower strength should be considered when designing ICFDPS on zirconia implants to reduce the risk of fractures along the intraosseous implant portion.

Toward therapeutic electrophysiology: beta-band suppression as a biomarker in chronic local field potential recordings.

Adaptive deep brain stimulation (aDBS) is a promising concept for feedback-based neurostimulation, with the potential of clinical implementation with the sensing-enabled Percept neurostimulator. We aim to characterize chronic electrophysiological activity during stimulation and to validate beta-band activity as a biomarker for bradykinesia. Subthalamic activity was recorded during stepwise stimulation amplitude increase OFF medication in 10 Parkinson's patients during rest and finger tapping. Offline analysis of wavelet-transformed beta-band activity and assessment of inter-variable relationships in linear mixed effects models were implemented. There was a stepwise suppression of low-beta activity with increasing stimulation intensity (p = 0.002). Low-beta power was negatively correlated with movement speed and predictive for velocity improvements (p < 0.001), stimulation amplitude for beta suppression (p < 0.001). Here, we characterize beta-band modulation as a chronic biomarker for motor performance. Our investigations support the use of electrophysiology in therapy optimization, providing evidence for the use of biomarker analysis for clinical aDBS.

Etiologies of insomnia in Parkinson's disease - Lessons from human studies and animal models.

Sleep disorders are integral to Parkinson's disease (PD). Insomnia, an inability to maintain stable sleep, affects most patients and is widely rated as one of the most debilitating facets of this disease. PD insomnia is often perceived as a multifactorial entity - a consequence of several of the disease symptoms, comorbidities and therapeutic strategies. Yet, this view evolved against a backdrop of a relative scarcity of works trying to directly dissect the underlying neural correlates and mechanisms in animal models. The last years have seen the emergence of a wealth of new evidence regarding the neural underpinnings of insomnia in PD. Here, we review early and recent reports from patients and animal models evaluating the etiology of PD insomnia. We start by outlining the phenomenology of PD insomnia and continue to analyze the evidence supporting insomnia as emanating from four distinct subdivisions of etiologies - the symptoms and comorbidities of the disease, the medical therapy, the degeneration of non-dopaminergic cell groups and subsequent alterations in circadian rhythms, and the degeneration of dopaminergic neurons in the brainstem and its resulting effect on the basal ganglia. Finally, we review emerging neuromodulation-based therapeutic avenues for PD insomnia.