Deep Brain Stimulation Programming 2.0: Future Perspectives for Target Identification and Adaptive Closed Loop Stimulation

Deep brain stimulation has developed into an established treatment for movement disorders and is being actively investigated for numerous other neurological as well as psychiatric disorders. An accurate electrode placement in the target area and the effective programming of DBS devices are considered the most important factors for the individual outcome. Recent research in humans highlights the relevance of widespread networks connected to specific DBS targets. Improving the targeting of anatomical and functional networks involved in the generation of pathological neural activity will improve the clinical DBS effect and limit side-effects. Here, we offer a comprehensive overview over the latest research on target structures and targeting strategies in DBS. In addition, we provide a detailed synopsis of novel technologies that will support DBS programming and parameter selection in the future, with a particular focus on closed-loop stimulation and associated biofeedback signals

Deep Brain Stimulation Programming 2.0: Future Perspectives for Target Identification and Adaptive Closed Loop Stimulation

Deep brain stimulation has developed into an established treatment for movement disorders and is being actively investigated for numerous other neurological as well as psychiatric disorders. An accurate electrode placement in the target area and the effective programming of DBS devices are considered the most important factors for the individual outcome. Recent research in humans highlights the relevance of widespread networks connected to specific DBS targets. Improving the targeting of anatomical and functional networks involved in the generation of pathological neural activity will improve the clinical DBS effect and limit side-effects. Here, we offer a comprehensive overview over the latest research on target structures and targeting strategies in DBS. In addition, we provide a detailed synopsis of novel technologies that will support DBS programming and parameter selection in the future, with a particular focus on closed-loop stimulation and associated biofeedback signals

Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies

Deep brain stimulation (DBS) has become the treatment of choice for advanced stages of Parkinson's disease, medically intractable essential tremor, and complicated segmental and generalized dystonia. In addition to accurate electrode placement in the target area, effective programming of DBS devices is considered the most important factor for the individual outcome after DBS. Programming of the implanted pulse generator (IPG) is the only modifiable factor once DBS leads have been implanted and it becomes even more relevant in cases in which the electrodes are located at the border of the intended target structure and when side effects become challenging. At present, adjusting stimulation parameters depends to a large extent on personal experience. Based on a comprehensive literature search, we here summarize previous studies that examined the significance of distinct stimulation strategies for ameliorating disease signs and symptoms. We assess the effect of adjusting the stimulus amplitude (A), frequency (f), and pulse width (pw) on clinical symptoms and examine more recent techniques for modulating neuronal elements by electrical stimulation, such as interleaving (Medtronic®) or directional current steering (Boston Scientific®, Abbott®). We thus provide an evidence-based strategy for achieving the best clinical effect with different disorders and avoiding adverse effects in DBS of the subthalamic nucleus (STN), the ventro-intermedius nucleus (VIM), and the globus pallidus internus (GPi)

Improving the Standard for Deep Brain Stimulation Therapy: Target Structures and Feedback Signals for Adaptive Stimulation. Current Perspectives and Future Directions

Deep brain stimulation (DBS) is an established therapeutic option for the treatment of various neurological disorders and has been used successfully in movement disorders for over 25 years. However, the standard stimulation schemes have not changed substantially. Two major points of interest for the further development of DBS are target-structures and novel adaptive stimulation techniques integrating feedback signals. We describe recent research results on target structures and on neural and behavioural feedback signals for adaptive deep brain stimulation (aDBS), as well as outline future directions

Subthalamic oscillatory activity and connectivity during gait in Parkinson's disease

Local field potentials (LFP) of the subthalamic nucleus (STN) recorded during walking may provide clues for determining the function of the STN during gait and also, may be used as biomarker to steer adaptive brain stimulation devices. Here, we present LFP recordings from an implanted sensing neurostimulator (Medtronic Activa PC+S) during walking and rest with and without stimulation in 10 patients with Parkinson's disease and electrodes placed bilaterally in the STN. We also present recordings from two of these patients recorded with externalized leads. We analyzed changes in overall frequency power, bilateral connectivity, high beta frequency oscillatory characteristics and gait-cycle related oscillatory activity. We report that deep brain stimulation improves gait parameters. High beta frequency power (20-30 Hz) and bilateral oscillatory connectivity are reduced during gait, while the attenuation of high beta power is absent during stimulation. Oscillatory characteristics are affected in a similar way. We describe a reduction in overall high beta burst amplitude and burst lifetimes during gait as compared to rest off stimulation. Investigating gait cycle related oscillatory dynamics, we found that alpha, beta and gamma frequency power is modulated in time during gait, locked to the gait cycle. We argue that these changes are related to movement induced artifacts and that these issues have important implications for similar research

Clostridium difficile ribotypes in Austria: a multicenter, hospital-based survey

A prospective, noninterventional survey was conducted among Clostridium difficile positive patients identified in the time period of July until October 2012 in 18 hospitals distributed across all nine Austrian provinces. Participating hospitals were asked to send stool samples or isolates from ten successive patients with C.difficile infection to the National Clostridium difficile Reference Laboratory at the Austrian Agency for Health and Food Safety for PCR-ribotyping and in vitro susceptibility testing. A total of 171 eligible patients were identified, including 73 patients with toxin-positive stool specimens and 98 patients from which C. difficile isolates were provided. Of the 159 patients with known age, 127 (74.3 %) were 65 years or older, the median age was 76 years (range: 9–97 years), and the male to female ratio 2.2. Among these patients, 73 % had health care-associated and 20 % community-acquired C. difficile infection (indeterminable 7 %). The all-cause, 30-day mortality was 8.8 % (15/171). Stool samples yielded 46 different PCR-ribotypes, of which ribotypes 027 (20 %), 014 (15.8 %), 053 (10.5 %), 078 (5.3 %), and 002 (4.7 %) were the five most prevalent. Ribotype 027 was found only in the provinces Vienna, Burgenland, and Lower Austria. Severe outcome of C. difficile infection was found to be associated with ribotype 053 (prevalence ratio: 3.04; 95 % CI: 1.24, 7.44), not with the so-called hypervirulent ribotypes 027 and 078. All 027 and 053 isolates exhibited in vitro resistance against moxifloxacin. Fluoroquinolone use in the health care setting must be considered as a factor favoring the spread of these fluoroquinolone resistant C. difficile clones

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG