Technological advances in deep brain stimulation:Towards an adaptive therapy

Parkinson's disease (PD) is neurodegenerative movement disorder and a treatment method called deep brain stimulation (DBS) may considerably reduce the patient’s motor symptoms. The clinical procedure involves the implantation of a DBS lead, consisting of multiple electrode contacts, through which continuous high frequency (around 130 Hz) electric pulses are delivered in the brain. In this thesis, I presented the research which had the goal to improve current DBS technology, focusing on bringing the conventional DBS system a step closer to adaptive DBS, a personalized DBS therapy. The chapters in this thesis can be seen as individual building blocks for such an adaptive DBS system. After the general introduction, the first two chapters, two novel DBS lead designs are studied in a computational model. The model showed that both studied leads were able to exploit the novel distribution of the electrode contacts to shape and steer the stimulation field to activate more neurons in the chosen target compared to the conventional lead, and to counteract lead displacement. In the fourth chapter, an inverse current source density (CSD) method is applied on local field potentials (LFP) measured in a rat model. The pattern of CSD sources can act as a landmark within the STN to locate the potential stimulation target. The fifth and final chapter described the last building block of the DBS system. We introduced an inertial sensors and force sensor based measurement system, which can record hand kinematics and joint stiffness of PD patients. A system which can act as a feedback signal in an adaptive DBS system

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming and overall management

Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics

The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including Parkinson’s disease, essential tremor, Tourette syndrome, epilepsy, cognitive disorders, and addiction. Each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. This year’s report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver DBS, ans improved neuroimaging techniques. The proceedings also offer insights into the new era of brain network neuromodulation and connectomic DBS to define and target dysfunctional brain networks. The proceedings also focused on innovations in applications and understanding of adaptive DBS (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for DBS indications. Finally, updates on neuroethical, legal, social, and policy issues relevant to DBS research are discussed

Electrocorticography is superior to subthalamic local field potentials for movement decoding in Parkinson’s disease

Brain signal decoding promises significant advances in the development of clinical brain computer interfaces (BCI). In Parkinson's disease (PD), first bidirectional BCI implants for adaptive deep brain stimulation (DBS) are now available. Brain signal decoding can extend the clinical utility of adaptive DBS but the impact of neural source, computational methods and PD pathophysiology on decoding performance are unknown. This represents an unmet need for the development of future neurotechnology. To address this, we developed an invasive brain-signal decoding approach based on intraoperative sensorimotor electrocorticography (ECoG) and subthalamic LFP to predict grip-force, a representative movement decoding application, in 11 PD patients undergoing DBS. We demonstrate that ECoG is superior to subthalamic LFP for accurate grip-force decoding. Gradient boosted decision trees (XGBOOST) outperformed other model architectures. ECoG based decoding performance negatively correlated with motor impairment, which could be attributed to subthalamic beta bursts in the motor preparation and movement period. This highlights the impact of PD pathophysiology on the neural capacity to encode movement vigor. Finally, we developed a connectomic analysis that could predict grip-force decoding performance of individual ECoG channels across patients by using their connectomic fingerprints. Our study provides a neurophysiological and computational framework for invasive brain signal decoding to aid the development of an individualized precision-medicine approach to intelligent adaptive DBS

The Expanding Horizon of Neural Stimulation for Hyperkinetic Movement Disorders

Novel methods of neural stimulation are transforming the management of hyperkinetic movement disorders. In this review the diversity of approach available is showcased. We first describe the most commonly used features that can be extracted from oscillatory activity of the central nervous system, and how these can be combined with an expanding range of non-invasive and invasive brain stimulation techniques. We then shift our focus to the periphery using tremor and Tourette's syndrome to illustrate the utility of peripheral biomarkers and interventions. Finally, we discuss current innovations which are changing the landscape of stimulation strategy by integrating technological advances and the use of machine learning to drive optimization

Adaptive Deep Brain Stimulation: From Experimental Evidence Toward Practical Implementation.

Closed-loop adaptive deep brain stimulation (aDBS) can deliver individualized therapy at an unprecedented temporal precision for neurological disorders. This has the potential to lead to a breakthrough in neurotechnology, but the translation to clinical practice remains a significant challenge. Via bidirectional implantable brain-computer-interfaces that have become commercially available, aDBS can now sense and selectively modulate pathophysiological brain circuit activity. Pilot studies investigating different aDBS control strategies showed promising results, but the short experimental study designs have not yet supported individualized analyses of patient-specific factors in biomarker and therapeutic response dynamics. Notwithstanding the clear theoretical advantages of a patient-tailored approach, these new stimulation possibilities open a vast and mostly unexplored parameter space, leading to practical hurdles in the implementation and development of clinical trials. Therefore, a thorough understanding of the neurophysiological and neurotechnological aspects related to aDBS is crucial to develop evidence-based treatment regimens for clinical practice. Therapeutic success of aDBS will depend on the integrated development of strategies for feedback signal identification, artifact mitigation, signal processing, and control policy adjustment, for precise stimulation delivery tailored to individual patients. The present review introduces the reader to the neurophysiological foundation of aDBS for Parkinson's disease (PD) and other network disorders, explains currently available aDBS control policies, and highlights practical pitfalls and difficulties to be addressed in the upcoming years. Finally, it highlights the importance of interdisciplinary clinical neurotechnological research within and across DBS centers, toward an individualized patient-centered approach to invasive brain stimulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Machine learning based brain signal decoding for intelligent adaptive deep brain stimulation

Sensing enabled implantable devices and next-generation neurotechnology allow real-time adjustments of invasive neuromodulation. The identification of symptom and disease-specific biomarkers in invasive brain signal recordings has inspired the idea of demand dependent adaptive deep brain stimulation (aDBS). Expanding the clinical utility of aDBS with machine learning may hold the potential for the next breakthrough in the therapeutic success of clinical brain computer interfaces. To this end, sophisticated machine learning algorithms optimized for decoding of brain states from neural time-series must be developed. To support this venture, this review summarizes the current state of machine learning studies for invasive neurophysiology. After a brief introduction to the machine learning terminology, the transformation of brain recordings into meaningful features for decoding of symptoms and behavior is described. Commonly used machine learning models are explained and analyzed from the perspective of utility for aDBS. This is followed by a critical review on good practices for training and testing to ensure conceptual and practical generalizability for real-time adaptation in clinical settings. Finally, first studies combining machine learning with aDBS are highlighted. This review takes a glimpse into the promising future of intelligent adaptive DBS (iDBS) and concludes by identifying four key ingredients on the road for successful clinical adoption: i) multidisciplinary research teams, ii) publicly available datasets, iii) open-source algorithmic solutions and iv) strong world-wide research collaborations.Fil: Merk, Timon. Charité – Universitätsmedizin Berlin; AlemaniaFil: Peterson, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Matemática Aplicada del Litoral. Universidad Nacional del Litoral. Instituto de Matemática Aplicada del Litoral; Argentina. Harvard Medical School; Estados UnidosFil: Köhler, Richard. Charité – Universitätsmedizin Berlin; AlemaniaFil: Haufe, Stefan. Charité – Universitätsmedizin Berlin; AlemaniaFil: Richardson, R. Mark. Harvard Medical School; Estados UnidosFil: Neumann, Wolf Julian. Charité – Universitätsmedizin Berlin; Alemani

Optimising programming to reduce side effects of subthalamic nucleus deep brain stimulation in Parkinson’s Disease

Subthalamic nucleus deep brain stimulation (STN DBS) is a widely used treatment for Parkinson’s disease patients with motor complications refractory to medical management. However, a significant proportion of treated patients suffer from stimulation induced side effects. Conventional options to address these by modulation of stimulation parameters and programming configurations have been limited. In recent years, technological advances have resulted in the emergence of novel programming features, including the use of short pulse width (PW) and directional steering, that represent further avenues to explore in this regard. In this thesis, I will present data on the utility of these programming techniques in alleviating stimulation induced side effects, and explore mechanisms that may mediate any observed effects. The data presented here is derived from four studies. Study 1 quantified the therapeutic window using short PW stimulation at 30μs relative to conventional 60μs settings. Study 2 represents a randomised controlled trial on short PW in chronic STN DBS patients with dysarthria. Study 3 evaluated the utility of directional steering, short PW, and the combination of these features in reversing stimulation induced dysarthria, dyskinesia, and pyramidal side effects. The findings of these studies suggest that short PW significantly increases the therapeutic window in terms of amplitude and charge, and that while it may not benefit chronic dysarthric patients collectively, directional steering and short PW can each significantly improve reversible stimulation induced side effects early in the course of STN DBS therapy. These novel techniques represent effective additional tools to conventional methods for optimising stimulation. In study 4, imaging and visualisation software are used to model and explore shifts in volume of tissue activated based on clinical data from study 3, and quantitatively compare charge per pulse, in order to explore potential mechanisms underlying the changes seen with these techniques