Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome.

BACKGROUND: The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD). OBJECTIVES: The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression. METHODS: Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features. RESULTS: We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling. CONCLUSIONS: A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Medial Subthalamic Nucleus Border as a New Anatomical Reference in Stereotactic Neurosurgery for Parkinson's Disease.

INTRODUCTION: The intersection of Bejjani's line with the well-delineated medial subthalamic nucleus (STN) border on MRI has recently been proposed as an individualized reference in subthalamic deep brain stimulation (DBS) surgery for Parkinson's disease (PD). We, therefore, aimed to investigate the applicability across centers of the medial STN border as a patient-specific reference point in STN DBS for PD and explore anatomical variability between left and right mesencephalic area within patients. Furthermore, we aim to evaluate a recently defined theoretic stimulation "hotspot" in a different center. METHODS: Preoperative 3-Tesla T2 and susceptibility-weighted images (SWI) were used to identify the intersection of Bejjani's line with the medial STN border in left and right mesencephalic area. The average stereotactic coordinates of the center of stimulation relative to the medial STN border were compared with the predefined theoretic stimulation "hotspot." RESULTS: Fifty-four patients provided 108 stereotactic coordinates of medial STN borders on both sequences. Significant difference in means was found in the Y-(anteroposterior) and Z-(dorsoventral) directions (T2 vs. SWI; p < 0.001). Mean coordinates in the Y-(anteroposterior) direction differed significantly between left and right mesencephalic area (T2: p < 0.001; SWI: p = 0.021). Sixty-six DBS leads were placed in 36 patients that had finished stimulation programming, and the average stereotactic coordinates of the center of stimulation relative to the medial STN border on T2 sequences were 3.1 mm lateral, 0.7 mm anterior, and 1.8 mm superior, in proximity of the predefined theoretic stimulation "hotspot." CONCLUSION: The medial STN border is applicable across centers as a reference point for STN DBS surgery for PD and seems suitable in order to account for interindividual and intraindividual anatomical variability if one is aware of the discrepancies between T2-weighted imaging and SWI.

Accuracy of Microelectrode Trajectory Adjustments during DBS Assessed by Intraoperative CT.

BACKGROUND/AIMS: Microelectrode recording (MER)-guided deep brain stimulation (DBS) aims to place the DBS lead in the optimal electrophysiological target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are made. The accuracy of these trajectory adjustments is unknown. Intraoperative computed tomography can visualize the microelectrode (ME) and verify ME adjustments. We aimed to determine the accuracy of ME movements in patients undergoing MER-guided DBS. METHODS: Coordinates following three methods of adjustment were compared: (1) those within the default "+" configuration of the ME holder; (2) those involving rotation of the default "+" to the "x" configuration; and (3) those involving head stage adjustments. Radial error and absolute differences between coordinates were determined. RESULTS: 87 ME movements in 59 patients were analyzed. Median (IQR) radial error was 0.59 (0.64) mm. Median (IQR) absolute x and y coordinate errors were 0.29 (0.52) and 0.38 (0.44) mm, respectively. Errors were largest after rotating the multielectrode holder to its "x"-shaped setup. CONCLUSION: ME trajectory adjustments can be made accurately. In a considerable number of cases, errors exceeding 1 mm were found. Adjustments from the "+" setup to the "x" setup are most prone to inaccuracies.

Borders of STN determined by MRI versus the electrophysiological STN. A comparison using intraoperative CT.

BACKGROUND: It is unclear which magnetic resonance imaging (MRI) sequence most accurately corresponds with the electrophysiological subthalamic nucleus (STN) obtained during microelectrode recording (MER, MER-STN). CT/MRI fusion allows for comparison between MER-STN and the STN visualized on preoperative MRI (MRI-STN). OBJECTIVE: To compare dorsal and ventral STN borders as seen on 3-Tesla T2-weighted (T2) and susceptibility weighted images (SWI) with electrophysiological STN borders in deep brain stimulation (DBS) for Parkinson's disease (PD). METHODS: Intraoperative CT (iCT) was performed after each MER track. iCT images were merged with preoperative images using planning software. Dorsal and ventral borders of each track were determined and compared to MRI-STN borders. Differences between borders were calculated. RESULTS: A total of 125 tracks were evaluated in 45 patients. MER-STN started and ended more dorsally than respective dorsal and ventral MRI-STN borders. For dorsal borders, differences were 1.9 ± 1.4 mm (T2) and 2.5 ± 1.8 mm (SWI). For ventral borders, differences were 1.9 ± 1.6 mm (T2) and 2.1 ± 1.8 mm (SWI). CONCLUSIONS: Discrepancies were found comparing borders on T2 and SWI to the electrophysiological STN. The largest border differences were found using SWI. Border differences were considerably larger than errors associated with iCT and fusion techniques. A cautious approach should be taken when relying solely on MR imaging for delineation of both clinically relevant STN borders.

Who May Benefit From On-Demand Control of Deep Brain Stimulation? Noninvasive Evaluation of Parkinson Patients.

BACKGROUND: In closed-loop on-demand control (ODC) of deep brain stimulation (DBS), stimulation is applied only when symptoms appear. Following stimulation of a fixed duration, DBS is switched off until the symptoms reappear. By repeating these demand-driven cycles, the amount of stimulation delivered can be decreased, thereby reducing DBS side-effects and improving battery-life of the pulse-generator. This article introduces Ro metric for quantification of degree of benefit of ODC and explores candidate selection in tremor-dominant Parkinson's disease (PD). METHOD: The study was performed on nine PD patients previously implanted with Medtronic DBS systems. Accelerometer sensor was placed on the tremor-dominant hand to detect onset of tremor. Fixed duration of stimulation (DS) of 20-80 sec was applied. Once the tremor was observed, stimulation was switched on. These trials were repeated during resting, postural, and kinetic conditions. Ro metric was calculated as the ratio of stimulation-off tremor-free period to the DS. Ro calculated at different DS were compared for each patient. RESULTS: We found that for each patient, Ro varied with DS and an optimal DS* gave a higher percentage of stimulation-off time. Average Ro at DS* varied from 0.554 to 4.24 for eight patients giving 35%-80% stimulation-off time. CONCLUSIONS: Ro values can be used for selection of optimal DS* in ODC. Three of nine patients were found to be tremor-free without stimulation for >50% of total time with even up to 80% in one patient. Patients with low Ro may not benefit from ODC in DBS, where the trade-off between having side-effects and using ODC system will need to be assessed.

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging.

OBJECTIVE: To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). BACKGROUND: Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. METHODS: DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. RESULTS: Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). CONCLUSION: Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary.

Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson's disease.

OBJECTIVES: This study was undertaken to compare efficacy, tolerability, and pharmacokinetics of DM-1992, an extended-release formulation of carbidopa/levodopa (CD/L-dopa) with immediate-release (IR) CD/L-dopa in patients with advanced Parkinson's disease. METHODS: This randomized, open-label, crossover study included a 3-d baseline and two 10-d treatment periods. Patients with daily OFF time of 2.5 h or more taking 400 mg or more L-dopa/d in four or more divided doses were titrated to stable regimens of DM-1992 2 times per day or CD/L-dopa IR 3 times to 8 times per day. Patients were allowed to take rescue CD/L-dopa as needed. Using home diaries, patients recorded OFF time and ON time with or without troublesome dyskinesia during baseline and treatment days 7 through 9. During 12-h clinic visits on day 10, plasma samples were collected for pharmacokinetics, and motor performance was assessed hourly. RESULTS: Thirty-four patients were enrolled; mean baseline L-dopa dosage was 968 mg/d. After titration, CD/L-dopa IR was dosed 4.8 times per day and DM-1992, 2 times per day. Rescue CD/L-dopa IR was given 1.3 times during the DM-1992 arm and 0.2 times during the CD/L-dopa IR arm. The reduction from baseline in % OFF time was greater for DM-1992 compared with CD/L-dopa IR (-5.52% vs. +1.33%; P = 0.0471). At steady-state, compared with CD/L-dopa IR, DM-1992 exhibited a smoother plasma L-dopa concentration profile mostly because of a significantly higher (day 10) predose L-dopa concentration, associated with enhanced motor performance. Although more patients taking DM-1992 had one or more adverse events (AEs) than CD/L-dopa IR patients (35% vs. 15%), no pattern to the AEs was seen, nor any resulting discontinuations. CONCLUSIONS: DM-1992 was associated with a reduction in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency. Although the open-label study design and the greater number of rescue doses during the DM-1992 arm call for caution in interpreting the results, the elevated predose plasma L-dopa concentration (12 h after DM-1992 administration) lends objective support to our findings, suggesting that phase 3 studies are warranted.

International validation of a behavioral scale in Parkinson's disease without dementia.

The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n=260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ=0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ=0.56); apathy with the Lille Apathy Rating Scale (ρ=0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia.

Analysis of Stereotactic Accuracy in Patients Undergoing Deep Brain Stimulation Using Nexframe and the Leksell Frame.

OBJECTIVE: To determine and compare the accuracy of Nexframe and the Leksell stereotactic frame in deep brain stimulation (DBS) procedures. BACKGROUND: The 'frameless' Nexframe uses bone fiducials rather than a head-mounted frame, which offers potential benefits for both the patient and the surgical team. Accuracy of lead implantation and factors affecting this accuracy are of crucial importance but have not been extensively studied for the frameless system. DESIGN/METHODS: The location of 194 (Leksell frame, n = 116; Nexframe, n = 78) DBS leads was determined on postoperative MRI. Obtained stereotactic coordinates were compared with expected intraoperative target coordinates. Resulting absolute errors in the X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (x0394;X, x0394;Y, and x0394;Z) were then used to calculate the vector error (VE). The vector error describes the total error in 3-D space and represents our main outcome measure. RESULTS: The vector error (mean ± SD) was 2.8 ± 1.3 for Nexframe and 2.5 ± 1.2 for the Leksell frame (p = 0.43). For Nexframe, absolute X, Y, and Z errors were 1.4 ± 1.3, 1.7 ± 1.2, and 1.0 ± 0.9 mm. For the Leksell frame, the absolute X, Y, and Z errors were 1.4 ± 1.0, 1.2 ± 1.0, and 1.3 ± 0.9 mm. On the anterior-posterior plane (Y coordinate), the Leksell frame was more accurate than Nexframe (p = 0.04). In contrast, Nexframe was more accurate on the dorsal-ventral plane (Z coordinate) (p = 0.04). There was no difference in accuracy between the two methods on the medial-lateral plane (X coordinate). CONCLUSION: This comparison of Nexframe and the Leksell frame shows that both techniques have equivalent overall 3-D accuracy.

Directional Deep Brain Stimulation Programming: Is the Segment Clearly Identifiable and Stable Over Time?

BACKGROUND: In our early experience programming directional deep brain stimulation (d-DBS) in PD, we found the optimal directional segment changed over time in some patients. To determine the frequency/reasons for this we examined whether (1) different programmers would identify the same segment as "optimal"; and (2) the same programmer would select the same "optimal" segment over time. We hypothesized there would be a moderately high level of agreement on optimal electrode selection between different assessors and repeated assessments by the same evaluator. METHODS: This was a prospective, double-blind investigation evaluating the reliability and stability of programming d-DBS. Each patient underwent a mono-polar survey four times (2 time points by 2 separate assessors). The primary aim was the inter-rater agreement of selecting the optimal electrode at 1 and 6 months. The secondary aim was to determine the intra-rater agreement of selecting the optimal electrode from 1 to 6 months. RESULTS: Twenty-one patients were enrolled. There was fair inter-rater agreement at 1 month and moderate at 6 months. There was minimal intra-rater agreement between 1 and 6 months. DISCUSSION: The data refuted our hypothesis. Potential reasons for low agreement include (1) the arduous/subjective nature of identifying the optimal electrode in d-DBS systems, especially in well-placed electrodes; and/or (2) acute changes to the location of stimulation delivery offering temporary improvement in symptoms. Key takeaways gathered were it may, (1) behoove the programmer to explore different electrode montages after a period of time; and (2) be more efficient to review the directional electrode montage only when dictated by clinical symptoms/disease progression.

Benefits of subthalamic nucleus deep brain stimulation on visually-guided saccades depend on stimulation side and classic paradigm in Parkinson's disease.

OBJECTIVE: We aimed to gain further insight into previously reported beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on visually-guided saccades by examining the effects of unilateral compared to bilateral stimulation, paradigm, and target eccentricity on saccades in individuals with Parkinson's disease (PD). METHODS: Eleven participants with PD and STN-DBS completed the visually-guided saccade paradigms with OFF, RIGHT, LEFT, and BOTH stimulation. Rightward saccade performance was evaluated for three paradigms and two target eccentricities. RESULTS: First, we found that BOTH and LEFT increased gain, peak velocity, and duration compared to OFF stimulation. Second, we found that BOTH and LEFT stimulation decreased latency during the gap and step paradigms but had no effect on latency during the overlap paradigm. Third, we found that RIGHT was not different compared to OFF at benefiting rightward saccade performance. CONCLUSIONS: Left unilateral and bilateral stimulation both improve the motor outcomes of rightward visually-guided saccades. Additionally, both improve latency, a cognitive-motor outcome, but only in paradigms when attention does not require disengagement from a present stimulus. SIGNIFICANCE: STN-DBS primarily benefits motor and cognitive-motor aspects of visually-guided saccades related to reflexive attentional shifting, with the latter only evident when the fixation-related attentional system is not engaged.

Medication only improves limb movements while deep brain stimulation improves eye and limb movements during visually-guided reaching in Parkinson's disease.

Background: Antiparkinson medication and subthalamic nucleus deep brain stimulation (STN-DBS), two common treatments of Parkinson's disease (PD), effectively improve skeletomotor movements. However, evidence suggests that these treatments may have differential effects on eye and limb movements, although both movement types are controlled through the parallel basal ganglia loops. Objective: Using a task that requires both eye and upper limb movements, we aimed to determine the effects of medication and STN-DBS on eye and upper limb movement performance. Methods: Participants performed a visually-guided reaching task. We collected eye and upper limb movement data from participants with PD who were tested both OFF and ON medication (n = 34) or both OFF and ON bilateral STN-DBS while OFF medication (n = 11). We also collected data from older adult healthy controls (n = 14). Results: We found that medication increased saccade latency, while having no effect on reach reaction time (RT). Medication significantly decreased saccade peak velocity, while increasing reach peak velocity. We also found that bilateral STN-DBS significantly decreased saccade latency while having no effect on reach RT, and increased saccade and reach peak velocity. Finally, we found that there was a positive relationship between saccade latency and reach RT, which was unaffected by either treatment. Conclusion: These findings show that medication worsens saccade performance and benefits reaching performance, while STN-DBS benefits both saccade and reaching performance. We explore what the differential beneficial and detrimental effects on eye and limb movements suggest about the potential physiological changes occurring due to treatment.

Intraoperative x-ray to measure distance between DBS leads: A reliability study.

BACKGROUND: Many factors can jeopardize the accuracy of deep brain stimulation (DBS) lead placement. Confirmation of lead placement while the patient is still in the operating room would be advantageous. Intraoperative MRI or CT can identify placement errors, but these modalities can be cost- or time prohibitive. Intraoperative fluoroscopy may give information on the accuracy of the Y coordinate, but the accuracy of the X coordinate usually cannot be confirmed. When an object of known dimensions is present in the brain, such as a unilateral DBS lead, its dimensions can be used to calculate unknown distances. The objective of this study was to determine if intraoperative AP skull x-ray accurately predicts the distance between DBS electrodes using postoperative MRI as the gold standard. METHODS: The distance between 32 pairs of DBS leads was measured by 2 independent raters under blinded conditions on intraoperative AP x-ray and postoperative axial and coronal MRI. Variable x-ray magnification was accounted for using the formula: actual distance between 2 leads = (measured distance between DBS leads)/(average measured length of electrodes) × 7.5 mm. RESULTS: The mean (± SD) distance on x-ray was 22.62 ± 2.23 mm, on axial MRI 22.78 ± 1.90 mm, and on coronal MRI 22.79 ± 2.00 mm. ANOVA revealed no difference based on method (P = .887) or raters (P = .940). The intraclass correlation coefficient showed excellent interrater reliability, CONCLUSIONS: Intraoperative AP x-ray accurately predicts the distance between DBS leads. The technique is especially useful when the location of the first DBS lead relative to the midline is known, such as during staged bilateral procedures or lead replacement procedures.

Long-Term Clinical Experience with Directional Deep Brain Stimulation Programming: A Retrospective Review.

INTRODUCTION: Directional deep brain stimulation (d-DBS) axially displaces the volume of tissue activated (VTA) towards the intended target and away from neighboring structures potentially improving benefit and reducing side effects (SE) of stimulation. A clinical trial evaluating d-DBS demonstrated a wider therapeutic window (TW) with directional electrodes. While this seems advantageous, it remains unclear when and why directional stimulation is chosen clinically. To evaluate the implementation of d-DBS in our practice we examined the prevalence of and motivation for directional programming. METHODS: A retrospective review was completed in consecutive patients with Parkinson's disease (PD)/essential tremor (ET) implanted with the Abbott Infinity system from December 2016 to January 2020. At 3, 12, 24, and 36 months we extracted post-DBS stimulation parameters; use of directional electrodes and other advanced programming techniques; and reasons for directional programming. RESULTS: Fifty-six patients with PD and 18 patients with ET (104 and 33 leads, respectively) were identified. The numbers of patients programmed with a directional electrode in at least one DBS lead in PD and ET, respectively, were 22/56 (39%) and 13/18 (72%) at 3 months; 19/48 (40%) and 8/12 (67%) at 12 months; 12/31 (39%) and 5/8 (63%) at 24 months; and 6/9 (67%) and 1/2 (50%) at 36 months. In PD and ET, reasons for using directional stimulation were better symptom control, less SE, or combination of better symptom control/SE; additional reasons in ET were improved battery/TW%. CONCLUSION: Over a 36-month time period 39-68% of patients with PD and 50-72% of patients with ET had at least one lead programmed directionally in order to either improve symptom control or reduce side effects, an option not available with conventional omnidirectional stimulation. Initially directional electrodes were used in ET more frequently than PD, likely because of the less complex nature of programming for a monosymptomatic disorder. However, over time this shifted as we gained directional experience and sought solutions to reduce worsening symptoms.

Medication adversely impacts visually-guided eye movements in Parkinson's disease.

OBJECTIVE: We examined whether previous inconsistent findings about the effect of anti-Parkinsonian medication on visually-guided saccades (VGS) were due to the use of different paradigms, which change the timing of fixation offset and target onset, or different target eccentricities. METHODS: Thirty-three participants with Parkinson's disease (PD) completed the VGS tasks OFF and ON medication, along with 13 healthy controls. Performance on 3 paradigms (gap, step, and overlap) and 2 target eccentricities was recorded. We used mixed models to determine the effect of medication, paradigm, and target eccentricity on saccade latency, gain, and peak velocity. RESULTS: First, we confirmed known paradigm effects on latency, and target eccentricity effects on gain and peak velocity in participants with PD. Second, latency was positively associated with OFF medication Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score in PD. Third, medication prolonged latency for the larger target eccentricity across the 3 paradigms, while decreasing gain and peak velocity in the step paradigm across target eccentricities. CONCLUSIONS: Medication adversely affected and was not therapeutically beneficial for VGS. Previous inconsistencies may have resulted from chosen target eccentricity. SIGNIFICANCE: The negative medication effect on VGS may be clinically significant, as many activities in daily life require oculomotor control, inhibitory control, and visually-guided shifts of attention.

Subthalamic Peak Beta Ratio Is Asymmetric in Glucocerebrosidase Mutation Carriers With Parkinson's Disease: A Pilot Study.

Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). Glucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD. Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non-GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity. Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non-GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity. Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.

Digital Health Integration With Neuromodulation Therapies: The Future of Patient-Centric Innovation in Neuromodulation.

Digital health can drive patient-centric innovation in neuromodulation by leveraging current tools to identify response predictors and digital biomarkers. Iterative technological evolution has led us to an ideal point to integrate digital health with neuromodulation. Here, we provide an overview of the digital health building-blocks, the status of advanced neuromodulation technologies, and future applications for neuromodulation with digital health integration.

Attenuated Postprandial GLP-1 Response in Parkinson's Disease.

The incretin hormone glucagon-like peptide 1 (GLP-1) has neuroprotective effects in animal models of Parkinson's disease (PD), and GLP-1 receptor agonists are associated with clinical improvements in human PD patients. GLP-1 is produced and secreted by intestinal L-cells in response to consumption of a meal. Specifically, intestinal microbiota produce short chain fatty acids (SCFA) which, in turn, promote secretion of GLP-1 into the systemic circulation, from which it can enter the brain. Our group and others have reported that PD patients have an altered intestinal microbial community that produces less SCFA compared to age-matched controls. In this report, we demonstrate that PD patients have diminished GLP-1 secretion in response to a meal compared to their household controls. Peak postprandial GLP-1 levels did not correlate with PD disease severity, motor function, or disease duration. These data provide the scientific rationale for future studies designed to elucidate the role of GLP-1 in the pathogenesis of PD and test the potential utility of GLP-1-directed therapies.