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Abstract Parkinson’s disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early- to mid-stage PD patients (N = 78) on Parkinsonian medication and age- and sex-matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power and central alpha frequency, beta power and central beta frequency, and 1/f broadband characteristics using power spectral density. Furthermore, we characterised transient oscillatory burst events in the mu-beta band time-domain signals. We examined the relationship between these signal features and the patients’ disease state, symptom severity, age, sex, and cortical thickness. PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, the burst rate was associated with increased severity of bradykinesia, whereas the burst duration was associated with axial symptoms. Our study shows that general non-oscillatory features (broadband 1/f exponent and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.

Abstract Parkinson’s disease (PD) is characterised by a loss of dopamine and dopaminergic cells. The consequences hereof are widespread network disturbances in brain function. It is an ongoing topic of investigation how the disease-related changes in brain function manifest in PD relate to clinical symptoms. We present The Swedish National Facility for Magnetoencephalography Parkinson’s Disease Dataset (NatMEG-PD) as an Open Science contribution to identify the functional neural signatures of Parkinson’s disease and contribute to diagnosis and treatment. The dataset contains whole-head magnetoencephalographic (MEG) recordings from 66 well-characterised PD patients on their regular dose of dopamine replacement therapy and 68 age- and sex-matched healthy controls. NatMEG-PD contains three-minute eyes-closed resting-state MEG, MEG during an active movement task, and MEG during passive movements. The data includes anonymised MRI for source analysis and clinical scores. MEG data is rich in nature and can be used to explore numerous functional features. By sharing these data, we hope other researchers will contribute to advancing our understanding of the relationship between brain activity and disease state or symptoms.

IntroductionVisual disturbance is common symptom in Parkinson’s disease (PD), and defective pupil light reflex (PLR) is an anticipated contributing factor that may be associated to the presence of autonomic dysfunction, which is a common non-motor feature of PD. Studies investigating the intercorrelation between PLR and dysautonomia in PD are limited.MethodsThe aim of this study was to investigate differences of PLR parameters, measured by eye-tracker, between patients with PD, with and without signs of dysautonomia, and healthy controls (HC). In total, 43 HC and 50 patients with PD were recruited and PLR parameters were measured with Tobii Pro Spectrum, during a long (1,000 ms) and a short (100 ms) light stimulus. Presence of orthostatic hypotension (OH) was used as proxy marker of dysautonomia. Linear mixed-effects model and non-parametric comparative statistics were applied to investigate differences among groups.ResultsPeak constriction velocity was slower in PD compared with HC, after adjustment for age and sex in the mixed model, and the difference was greater in the subgroup of PD with OH (unadjusted). Dilation amplitude and velocity were also gradually slower in HC vs. PD without OH vs. PD with OH (unadjusted for confounders). In the mixed model, age was significant predictor of dilation response.DiscussionOur results support previous observations on defective PLR in PD, evaluated with eye-tracker, and show a possible association with autonomic dysfunction. Further studies with more patients and rigorous evaluation of autonomic dysfunction are needed to validate these findings.

Abstract Introduction Gaucher disease (GD) is a monogenic, lysosomal storage disorder, classified according to the presence of acute (type 2), chronic (type 3), or no (type 1) neurological manifestations. The Norrbottnian subtype of neuronopathic GD type 3 (GD3) is relatively frequent in the northern part of Sweden. It exhibits a wide range of neurological symptoms but is characterized by extended life expectancy compared to GD3 in other countries. The aim of our study was to describe the cognitive profile of adult patients with Norrbottnian GD3. Materials and Methods Ten patients with GD3 (five males and five females) underwent neurocognitive testing with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RBANS consists of different short tests that assess Immediate Memory, Visuospatial and Constructional function, Language, Attention, and Delayed Memory. General neurological symptoms of the patients were assessed with the modified severity scoring tool. Results Patients (median age 41.5 range 24–57) performed lower than average in all cognitive domains. The overall index score was low (median 58.5, Interquartile range [IQR] 25.5), with the most profound deficit in attention (median 57, IQR 32.5) and immediate memory (median 76.5, IQR 13). Higher scores were found in language (median 83, IQR 21.5), delayed memory (median 81, IQR 41), and visuospatial/constructional function (median 86, IQR 32.35). Conclusion Norrbottnian GD3 patients showed a unique neurocognitive profile with low overall performance, mostly derived from low scores in attention and memory domains whereas language and visuospatial/constructional ability were relatively spared.

While deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinson’s disease (PD), it may also increase impulsivity by interfering with the inhibition of reflexive responses. The aim of this study was to investigate if varying the pulse frequency of STN-DBS has a modulating effect on response inhibition and its neural correlates.For this purpose, 14 persons with PD repeated an antisaccade task in three stimulation settings (DBS off, high-frequency DBS (130 Hz), mid-frequency DBS (60 Hz)) in a randomized order, while eye movements and brain activity via high-density EEG were recorded.On a behavioral level, 130 Hz DBS stimulation had no effect on response inhibition measured as antisaccade error rate, while 60 Hz DBS induced a slight but significant reduction of directional errors compared with the DBS-off state and 130 Hz DBS. Further, stimulation with both frequencies decreased the onset latency of correct antisaccades, while increasing the latency of directional errors.Time-frequency domain analysis of the EEG data revealed that 60 Hz DBS was associated with an increase in preparatory theta power over a midfrontal region of interest compared with the off-DBS state which is generally regarded as a marker of increased cognitive control. While no significant differences in brain activity over mid- and lateral prefrontal regions of interest emerged between the 60 Hz and 130 Hz conditions, both stimulation frequencies were associated with a stronger midfrontal beta desynchronization during the mental preparation for correct antisaccades compared with DBS off-state which is discussed in the context of potentially enhanced proactive recruitment of the oculomotor network.Our preliminary findings suggest that mid-frequency STN-DBS may provide beneficial effects on response inhibition, while both 130 Hz- and 60 Hz STN-DBS may promote voluntary actions at the expense of slower reflexive responses.

Background: The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. Objective: The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. Methods: Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. Results: Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. Conclusions: Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.

Postural instability marks a prevalent symptom of Parkinson’s disease (PD). It often manifests in increased body sway, which is commonly assessed by tracking the Center of Pressure (CoP). Yet, in terms of postural control, the body’s Center of Mass (CoM), and not CoP is what is regulated in a gravitational field. The aim of this study was to explore the effect of early- to mid-stage PD on these measures of postural control in response to unpredictable visual perturbations. We investigated three cohorts: (i) 18 patients with early to mid-stage PD [Hoehn & Yahr stage (1–3); 1.94 ± 0.70]; (ii) a group of 15 age-matched controls (ECT); and (iii) a group of 12 young healthy adults (YCT). Participants stood on a force plate to track their CoP, while the movement of their entire body was recorded with a video-based motion tracking system to monitor their CoM. A moving room paradigm was applied through a head-mounted virtual reality headset. The stimulus consisted of a virtual tunnel that stretched in the anterior-posterior direction which either remained static or moved back and forth in an unpredictable fashion.We found differences in mean sway amplitude (MSA) and mean velocities of CoP and CoM between the groups under both conditions, with higher MSA of CoP and CoM for PD and higher mean velocities of both variables for PD and ECT when compared with YCT. Visual perturbation increased mean CoP velocity in all groups but did not have effects on mean CoM velocity or MSA. While being significantly lower for the young adults, the net effect of visual perturbation on mean CoP velocity was similar between patients with PD and age-matched controls. There was no effect of the visual perturbation on mean CoM velocity for any of the groups.Our simultaneous assessment of CoP and CoM revealed that postural control is reflected differently in CoM and CoP. As the motion of CoM remained mostly unaffected, all groups successfully counteracted the perturbation and maintained their balance. Higher CoP velocity for PD and ECT revealed increased corrective motion needed to achieve this, which however was similar in both groups. Thus, our results suggest increased effort, expressed in CoP velocity, to be an effect of age rather than disease in earlier stages of PD.

Background: Recognizing emotional facial expressions is crucial for social interactions. Cognitive impairment and oculomotor abnormalities are common features of Parkinson's disease (PD) which may contribute to the performance in facial emotion recognition (FER) in PD. Objective: The aim of this study was to analyze eye movement behavior during a facial emotion recognition (FER) task with respect to cognitive state in PD patients and healthy controls. Methods: Eye movements of 24 non-demented, non-depressed PD patients (12 with intact cognitive functions and 12 with Mild Cognitive Impairment (MCI) according to MDS task force criteria level 2), and 12 age-, sex and education-matched healthy controls were recorded during visual exploration of 28 emotional (happiness, surprise, disgust, anger, fear and sadness) and neutral faces. Participants were asked to identify the displayed emotion out of a sevenfold multiple choice question. Results: PD-MCI patients showed reduced FER with specific impairment of anger recognition. Although the scanned area of PD patients with intact cognition was significantly restricted, they did not differ in FER from healthy subjects. While healthy subjects and cognitively intact PD patients scanned faces with preference for mouth and eyes, patients with PD-MCI tended to look at the center of the face and spent significantly less time fixating the mouth. Conclusions: Ineffective visual exploration may contribute to impaired emotion recognition in PD. Visual scanning of emotional faces is altered in PD even in the absence of cognitive impairment. The progression to PD-MCI may result in further deterioration of scanning behavior and FER impairment.

Background: Patients with Parkinson’s disease (PD) show eye movement abnormalities and frequently complain about difficulties in reading. So far, it is unclear whether basal ganglia dysfunction or cognitive impairment has a greater impact on eye movements during reading.Objective: To analyze eye movement behavior during a natural reading task with respect to cognitive state and dopaminergic therapy in PD and healthy controls.Methods: Eye movements of 59 PD patients and 29 age- and education-matched healthy controls were recorded during mute, self-paced reading of a text. 25 cognitively normal PD patients performed the task additionally in off medication state. Clinical assessment included a comprehensive neuropsychological test battery and the motor section of MDS—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).Results: PD-mild cognitive impairment (MCI) was diagnosed in 21 patients. Reading speed was significantly reduced in PD-MCI compared to healthy controls and PD patients without MCI due to higher numbers of progressive saccades. Cognitively intact PD patients showed no significant alterations of reading speed or eye movement pattern during reading. The fixation duration tended to be prolonged in PD compared to healthy controls and decreased significantly after levodopa intake. Scores for executive functions, attention, and language correlated with reading speed in the PD group.Conclusion: The present study is the first to reveal (1) reduced reading speed with altered reading pattern in PD with MCI and (2) a relevant impact of levodopa on fixation duration during reading in PD. Further research is needed to determine whether therapeutic interventions, e.g., levodopa or neuropsychological training, improve the subjective reading experience for patients with PD.

Background and study aims Conventional endoscopic retrograde cholangiopancreatography (ERCP) is hampered by two-dimensional visualization, post-procedural adverse events (AEs), and exposure to ionizing radiation. Bimodal ERCP might mitigate these challenges, but no reports of its use are available to date. The aim of this study was to explore the feasibility of bimodal ERCP, while investigating its potential clinical yield. Patients and methods This was a retrospective observational study of patients that underwent bimodal ERCP in a single tertiary academic referral center. Thirteen patients undergoing conventional ERCP had a previously T2-weighted isotropic 3 D TSE MRCP sequence aligned and fused with the two-dimensional image generated from the fluoroscopy c-arm unit in real time. Results Over a 2-month period, 13 patients with a mean age of 54 underwent bimodal ERCP for bile duct stricture (61.5 %), complex cholelithiasis (7.7 %) and ductal leakage (30.1 %). Bimodal ERCP was feasible in all 13 cases, and image quality was assessed as “good” in 11 patients (84.6 %). Bimodal ERCP aided in visualizing the lesion of interest (76.9 %), assisted in understanding the 3 D anatomy of the biliopancreatic ductal system (61.5 %), and aided in finding a favorable position for the c-arm (38.4 %) for subsequent therapeutic intervention. Conclusions This first report on bimodal ERCP proves its feasibility and suggests that it may assist in increasing both the diagnostic and therapeutic yield of ERCP, while at the same time decreasing AEs during and after ERCP. Its main application might lie in treatment of complex intrahepatic disease.

Introduction: Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non‐lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta‐analysis assessing the efficacy/effectiveness and safety of non‐lesional treatments for tremor in iPD. Methods: Three electronic databases were searched using a combination of title/abstract keywords complemented by hand‐searching of reference lists. A random‐effects meta‐analysis of standardized mean change scores was conducted where appropriate. Results: Some 114 studies met inclusion criteria involving 8045 patients. The meta‐analysis revealed an overall reduction of standardized mean change scores by (−0.93 [CI: −1.42; −0.43], p < 0.001) by 14 different dopaminergic and non‐dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non‐pharmacological interventions for tremor, except for electrical stimulation. Conclusions: The results of this meta‐analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high‐quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non‐lesional treatments in cases with refractory tremor is lacking. [ABSTRACT FROM AUTHOR]