In Parkinson’s disease (PD), subthalamic nucleus (STN) beta burst activity is pathologically elevated. These bursts are reduced by dopamine and deep brain stimulation (DBS). Therefore, these bursts have been tested as a trigger for closed-loop DBS. To provide better targeted parameters for closed-loop stimulation, we investigate the spatial distribution of beta bursts within the STN and if they are specific to a beta sub-band. Local field potentials (LFP) were acquired in the STN of 27 PD patients while resting. Based on the orientation of segmented DBS electrodes, the LFPs were classified as anterior, postero-medial, and postero-lateral. Each recording lasted 30 min with (ON) and without (OFF) dopamine. Bursts were detected in three frequency bands: ±3 Hz around the individual beta peak frequency, low beta band (lBB), and high beta band (hBB). Medication reduced the duration and the number of bursts per minute but not the amplitude of the beta bursts. The burst amplitude was spatially modulated, while the burst duration and rate were frequency dependent. Furthermore, the hBB burst duration was positively correlated with the akinetic-rigid UPDRS III subscore. Overall, these findings on differential dopaminergic modulation of beta burst parameters suggest that hBB burst duration is a promising target for closed-loop stimulation and that burst parameters could guide DBS programming.
The implantation of deep brain stimulation (DBS) electrodes in Parkinson's disease (PD) patients can lead to a temporary improvement in motor symptoms, known as the stun effect. However, the network alterations induced by the stun effect are not well characterized. As therapeutic DBS is known to alter resting-state networks (RSN) and subsequent motor symptoms in patients with PD, we aimed to investigate whether the DBS-related stun effect also modulated RSNs. Therefore, we analyzed RSNs of 27 PD patients (8 females, 59.0 +- 8.7 years) using magnetoencephalography and compared them to RSNs of 24 age-matched healthy controls (8 females, 62.8 +- 5.1 years). We recorded 30 min of resting-state activity two days before and one day after implantation of the electrodes with and without dopaminergic medication. RSNs were determined by use of phase-amplitude coupling between a low frequency phase and a high gamma amplitude and examined for differences between conditions (i.e., pre vs post surgery). We identified four RSNs across all conditions: sensory-motor, visual, fronto-occipital, and frontal. Each RSN was altered due to electrode implantation. Importantly, these changes were not restricted to spatially close areas to the electrode trajectory. Interestingly, pre-operative RSNs corresponded better with healthy control RSNs regarding the spatial overlap, although the stun effect is associated with motor improvement. Our findings reveal that the stun effect induced by implantation of electrodes exerts brain wide changes in different functional RSNs.
Recent evidence suggests that beta bursts in subthalamic nucleus (STN) play an important role in Parkinsonian pathophysiology. We studied the spatio-temporal relationship between STN beta bursts and cortical activity in 26 Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Postoperatively, we simultaneously recorded STN local field potentials (LFP) from externalized DBS leads and cortical activity using whole-brain magnetoencephalography. Event-related magnetic fields (ERF) were averaged time-locked to STN beta bursts and subjected to source localization. Our results demonstrate that ERF exhibiting activity significantly different from baseline activity were localized within areas functionally related to associative, limbic, and motor systems as well as regions pertinent for visual and language processing. Our data suggest that STN beta bursts are involved in network formation between STN and cortex. This interaction is in line with the idea of parallel processing within the basal ganglia-cortex loop, specifically within the functional subsystems of the STN (i.e., associative, limbic, motor, and the related cortical areas). ERFs within visual and language-related cortical areas indicate involvement of beta bursts in STN-cortex networks beyond the associative, limbic, and motor loops. In sum, our results highlight the involvement of STN beta bursts in the formation of multiple STN - cortex loops in patients with PD.
Deep brain stimulation (DBS), but also the sole implantation of the electrodes and dopaminergic medication, can reduce symptoms in Parkinson's disease (PD) patients. Furthermore, an effect on network activity is known for all three options separately. However, long-term effects have rarely been investigated. Therefore, in the present study, we focus on the long-term impact of dopaminergic medication on whole-brain network activity following DBS electrode implantation. Therefore, we extracted resting state networks (RSNs) of 20 PD patients (4 females, (59.00 ± 9.72 years) from magnetoencephalography data. We recorded 30 min of resting-state activity two days before and one year after implantation of the electrodes with and without dopaminergic medication, but DBS was turned off. RSNs were obtained based on the phase-amplitude coupling between a low-frequency phase and a high gamma amplitude and examined for differences between conditions (i.e., pre- vs. post-surgery). We identified three RSNs across all conditions: sensory-motor, visual, and frontal. Each RSN was selectively altered due to a year of disease progression - while patients being treated with dopaminergic medication and DBS. In line with previous literature, we focus on longitudinal changes in RSNs over time after electrode implantation, acknowledging that chronic DBS treatment and other factors may confound the interpretation of these changes. In addition, the alterations found were RSN specific, as dopaminergic medication showed a greater impact on the frontal RSN, and the longitudinal factor expressed by the disease progression was more severe in alterations in the SMN and the visual RSN.
1 January 2017 in Biomedical Engineering / Biomedizinische Technik
Background and Objectives: Clinical decision support systems (CDSS) can combine laboratory findings with additional clinical information to support diagnostic and therapeutic decision-making. This review characterizes the objectives of CDSS with relevance to laboratory medicine and examines the current evidence across six predefined domains: clinical maturity, type of evaluation, strength of evidence, integration potential, relevance to personalized medicine, and demonstrated medical benefit. Methods: PubMed was systematically searched for publications on CDSS with relevance to laboratory medicine published between 1 October 2019 and 31 August 2025. Publications without a specific laboratory-related component were excluded, and the detailed analysis was restricted to original publications. The 75 included publications were independently classified and assessed by the authors according to predefined criteria. Results were synthesized descriptively using absolute and relative frequencies across the predefined categories. Results: Publication activity showed an overall increase over the study period. The most common CDSS objectives were diagnostic support (25/75; 33%), therapy monitoring (14/75; 19%), and prognostic assessment (13/75; 17%). Only twelve publications (16%) investigated CDSS that provided specific recommendations for further diagnostic testing or therapy. Most evaluations were retrospective (31/75; 41%) or based on simulations and modelling (16/75; 21%); 13 publications (17%) used prospective non-randomized designs, and three (4%) described randomized designs, two of which were study protocols. In terms of clinical maturity, 45 CDSS were classified as experimental, six as prototypes, and 15 as clinically implemented. High integration potential was identified in 24 of the 75 publications (32%). Twenty publications (27%) met the predefined criteria for a positive effect on process or proxy parameters, and two met the criteria for clinical benefit; no publication demonstrated improvements in hard clinical endpoints. Only eight CDSS (11%) showed high relevance to personalized medicine. Conclusions: CDSS with relevance to laboratory medicine represent an active area of research. However, most systems remain at an early stage of development and have been insufficiently validated under real-world conditions. Sustainable clinical implementation will require prospective multicenter studies, patient-relevant endpoints, interoperable technical infrastructures, and stronger interdisciplinary involvement of laboratory medicine.