Project description:Epidural spinal cord stimulation (SCS) is currently proposed to treat intractable neuropathic pain. Since the 1970s, isolated cases and small cohorts of patients suffering from dystonia, tremor, painful leg and moving toes (PLMT), or Parkinson’s disease were also treated with SCS in the context of exploratory clinical studies. Despite the safety profile of SCS observed in these various types of movement disorders, the degree of improvement of abnormal movements following SCS has been heterogeneous among patients and across centers in open-label trials, stressing the need for larger, randomized, double-blind studies. This article provides a comprehensive review of both experimental and clinical studies of SCS application in movement disorders.
Project description:Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson's disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.
Project description:Electron paramagnetic resonance (EPR) and, more recently, solid-state nuclear magnetic resonance (NMR) have been employed to study photosynthetic processes, primarily related to the light-induced charge separation. Information obtained on the electronic structure, the relative orientation of the cofactors, and the changes in structure during these reactions should help to understand the efficiency of light-induced charge separation. A short introduction to the observables derived from magnetic resonance experiments is given. The relation of these observables to the electronic structure is sketched using the nitroxide group of spin labels as a simple example.
Project description:IntroductionRecent studies suggest that repeated transcranial magnetic stimulation (TMS) improves functional movement disorders (FMDs), but the underlying mechanisms are unclear. The objective was to determine whether the beneficial action of TMS in patients with FMDs is due to cortical neuromodulation or rather to a cognitive-behavioral effect.MethodConsecutive patients with FMDs underwent repeated low-frequency (0.25 Hz) magnetic stimulation over the cortex contralateral to the symptoms or over the spinal roots [root magnetic stimulation (RMS)] homolateral to the symptoms. The patients were randomized into two groups: group 1 received RMS on day 1 and TMS on day 2, while group 2 received the same treatments in reverse order. We blindly assessed the severity of movement disorders before and after each stimulation session.ResultsWe studied 33 patients with FMDs (dystonia, tremor, myoclonus, Parkinsonism, or stereotypies). The median symptom duration was 2.9 years. The magnetic stimulation sessions led to a significant improvement (>50%) in 22 patients (66%). We found no difference between TMS and RMS.ConclusionWe suggest that the therapeutic benefit of TMS in patients with FMDs is due more to a cognitive-behavioral effect than to cortical neuromodulation.
Project description:Patients with movement disorders treated by deep brain stimulation do not always achieve successful therapeutic alleviation of motor symptoms, even in cases where surgery is without complications. Magnetic resonance imaging (MRI) offers methods to investigate structural brain-related factors that may be predictive of clinical motor outcomes. This review aimed to identify features which have been associated with variability in clinical post-operative motor outcomes in patients with Parkinson's disease, dystonia, and essential tremor from structural MRI modalities. We performed a literature search for articles published between 1 January 2000 and 1 April 2022 and identified 5197 articles. Following screening through our inclusion criteria, we identified 60 total studies (39 = Parkinson's disease, 11 = dystonia syndromes and 10 = essential tremor). The review captured a range of structural MRI methods and analysis techniques used to identify factors related to clinical post-operative motor outcomes from deep brain stimulation. Morphometric markers, including volume and cortical thickness were commonly identified in studies focused on patients with Parkinson's disease and dystonia syndromes. Reduced metrics in basal ganglia, sensorimotor and frontal regions showed frequent associations with reduced motor outcomes. Increased structural connectivity to subcortical nuclei, sensorimotor and frontal regions was also associated with greater motor outcomes. In patients with tremor, increased structural connectivity to the cerebellum and cortical motor regions showed high prevalence across studies for greater clinical motor outcomes. In addition, we highlight conceptual issues for studies assessing clinical response with structural MRI and discuss future approaches towards optimizing individualized therapeutic benefits. Although quantitative MRI markers are in their infancy for clinical purposes in movement disorder treatments, structural features obtained from MRI offer the powerful potential to identify candidates who are more likely to benefit from deep brain stimulation and provide insight into the complexity of disorder pathophysiology.
Project description:Deep brain stimulation (DBS) is a neurosurgical technique, which consists of continuous delivery of an electrical pulse through chronically implanted electrodes connected to a neurostimulator, programmable in amplitude, pulse width, frequency, and stimulation channel. DBS is a promising treatment option for addressing severe and drug-resistant movement disorders. The success of DBS therapy is a combination of surgical implantation techniques, device technology, and clinical programming strategies. Changes in device settings require highly trained and experienced clinicians to achieve maximal therapeutic benefit for each targeted symptom, and optimization of stimulation parameters can take many visits. Thus, the development of innovative DBS technologies that can optimize the clinical implementation of DBS will lead to wider scale utilization. This review aims to present engineering approaches that have the potential to improve clinical outcomes of DBS, focusing on the development novel temporal patterns, innovative electrode designs, computational models to guide stimulation, closed-loop DBS, and remote programming.
Project description:Objective. Thresholding of neural responses is central to many applications of transcranial magnetic stimulation (TMS), but the stochastic aspect of neuronal activity and motor evoked potentials (MEPs) challenges thresholding techniques. We analyzed existing methods for obtaining TMS motor threshold and their variations, introduced new methods from other fields, and compared their accuracy and speed.Approach. In addition to existing relative-frequency methods, such as the five-out-of-ten method, we examined adaptive methods based on a probabilistic motor threshold model using maximum-likelihood (ML) or maximuma-posteriori(MAP) estimation. To improve the performance of these adaptive estimation methods, we explored variations in the estimation procedure and inclusion of population-level prior information. We adapted a Bayesian estimation method which iteratively incorporated information of the TMS responses into the probability density function. A family of non-parametric stochastic root-finding methods with different convergence criteria and stepping rules were explored as well. The performance of the thresholding methods was evaluated with an independent stochastic MEP model.Main Results. The conventional relative-frequency methods required a large number of stimuli, were inherently biased on the population level, and had wide error distributions for individual subjects. The parametric estimation methods obtained the thresholds much faster and their accuracy depended on the estimation method, with performance significantly improved when population-level prior information was included. Stochastic root-finding methods were comparable to adaptive estimation methods but were much simpler to implement and did not rely on a potentially inaccurate underlying estimation model.Significance. Two-parameter MAP estimation, Bayesian estimation, and stochastic root-finding methods have better error convergence compared to conventional single-parameter ML estimation, and all these methods require significantly fewer TMS pulses for accurate estimation than conventional relative-frequency methods. Stochastic root-finding appears particularly attractive due to the low computational requirements, simplicity of the algorithmic implementation, and independence from potential model flaws in the parametric estimators.
Project description:Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.
Project description:Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique uniquely equipped to both examine and modulate neural systems and related cognitive and behavioral functions in humans. As an examination tool, TMS can be used in combination with EEG (TMS-EEG) to elucidate directly, objectively, and noninvasively the intrinsic properties of a specific cortical region, including excitation, inhibition, reactivity, and oscillatory activity, irrespective of the individual's conscious effort. Additionally, when applied in repetitive patterns, TMS has been shown to modulate brain networks in healthy individuals, as well as ameliorate symptoms in individuals with psychiatric disorders. The key role of TMS in assessing and modulating neural dysfunctions and associated clinical and cognitive deficits in psychiatric populations is therefore becoming increasingly evident. In this article, the authors review TMS-EEG studies in schizophrenia and mood disorders, as most TMS-EEG studies to date have focused on individuals with these disorders. The authors present the evidence on the efficacy of repetitive TMS (rTMS) and theta burst stimulation (TBS), when targeting specific cortical areas, in modulating neural circuits and ameliorating symptoms and abnormal behaviors in individuals with psychiatric disorders, especially when informed by resting-state and task-related neuroimaging measures. Examples of how the combination of TMS-EEG assessments and rTMS and TBS paradigms can be utilized to both characterize and modulate neural circuit alterations in individuals with psychiatric disorders are also provided. This approach, along with the evaluation of the behavioral effects of TMS-related neuromodulation, has the potential to lead to the development of more effective and personalized interventions for individuals with psychiatric disorders.