Topics in Neuromodulation Treatment

"Topics in Neuromodulation Treatment" is a book that invites to the reader to make an update in this important and well-defined area involved in the Neuroscience world. The book pays attention in some aspects of the electrical therapy and also in the drug delivery management of several neurological illnesses including the classic ones like epilepsy, Parkinson's disease, pain, and other indications more recently incorporated to this important tool like bladder incontinency, heart ischemia and stroke. The manuscript is dedicated not only to the expert, but also to the scientist that begins in this amazing field. The authors are physicians of different specialties and they guarantee the clinical expertise to provide to the reader the best guide to treat the patient

Doctor of Philosophy

dissertationToday, we are implanting electrodes into many different parts of the peripheral and central nervous systems for the purpose of restoring function to people with nerve injury or disease. As technology and manufacturing continue to become more advanced, ne

Surgical Neurostimulation for Spinal Cord Injury.

Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI

Closing the Loop: Exploring the Use of Sacral Dorsal Root Ganglia Signals for Adaptive Neuromodulation of Bladder Function

Overactive bladder (OAB) is a highly prevalent condition which negatively affects the physical and mental health of millions of people worldwide. Sacral neuromodulation (SNM) is a third-line therapy that provides improved efficacy and less adherence issues as compared to conventional treatments. There have been ~300,000 SNM implants since the therapy was first introduced over 20 years ago. While SNM is delivered in an open-loop fashion, the therapy could have improved clinical efficacy by adopting a closed-loop stimulation paradigm that uses objective physiological feedback. One promising approach to obtain such feedback is by tapping into the nervous system that innervates the bladder. This dissertation focuses on using sacral level dorsal root ganglia (DRG) neural signals to provide sensory feedback for adaptive SNM a feline model. This work began with exploring machine learning algorithms and feature selection methods for bladder pressure decoding in an offline analysis of DRG signals. A Kalman filter delivered the highest performance based on correlation coefficient between the pressure measurements and algorithm estimation. Additionally, firing rate normalization significantly contributed to lowering the normalized error, and a correlation coefficient-based channel selection method provided the lowest error compared to other channel selection methods. Following algorithm optimization, this work implemented the optimized algorithm and feature selection method in real-time in anesthetized healthy bladder and simulated OAB feline models. A 0.88 ± 0.16 decoding correlation coefficient fit was achieved by the algorithm across 35 normal and simulated OAB bladder fill sequences in five experiments. Additionally, closed-loop neuromodulation was demonstrated using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials. Finally, closed-loop SNM with the DRG sensory feedback algorithm was performed in anesthetized experiments. Our approach increased bladder capacity by 13.8% over no stimulation (p < 0.001). While there was no statistical difference in bladder capacity between closed-loop and continuous stimulation (p = 0.80), closed-loop stimulation reduced stimulation time by 57.7%. Interestingly, clearly-identified bladder single units had a reduced sensitivity during stimulation, suggesting a potential mechanism of SNM. This dissertation also developed a method for chronic behavioral monitoring and neuromodulation of bladder function in a feline model. We tracked urodynamic parameters across multiple week testing intervals. We observed that animals could tolerate pudendal nerve stimulation above motor threshold. Interestingly, stimulation at 5 and 33 Hz appeared to have a modulatory effect on voiding interval and efficiency in line with prior work under anesthesia. Overall, this work demonstrated that sacral level DRG are a viable sensory feedback target for adaptive SNM. This dissertation also investigated a behavioral paradigm that will be useful for system validation in awake and chronic experiments. Behavioral experiments such as these, as well as development of low-power systems for adaptive monitoring and feedback, are a crucial step prior to clinical translation of this method. Ultimately, implementation of closed-loop adaptive SNM will lead to an improved therapy and greater potential benefit for the millions of individuals with OAB.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/166129/1/aileenou_1.pd

Precision neuromodulation: Promises and challenges of spinal stimulation for multi-modal rehabilitation

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar presentations when developing spinal stimulation-based therapies. We also motivate advancement of multi-modal rehabilitation paradigms, which leverage the dense interconnectivity of sensorimotor spinal networks and the unique ability of electrical stimulation to modulate these networks to facilitate and guide simultaneous rehabilitation across domains

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue